The graviola impact on human astroglioma cells: functional significance of MUDENG

Graviola (Annona muricate) is a coveted tropical plant that has been found to be effective against many human cancers. Malignant glioblastoma multiformes are the most common and aggressive malignant forms of astrocytoma in the central nervous system. MUDENG (Mu-2-related death-inducing gene, MuD) is involved in cell death signaling. In this study, we investigated the impact of extracts from graviola leaves (from Korea and Africa), fruits and seeds against human astroglioma cells. Interestingly, graviola leaf extract-Korea (GLE-K), graviola leaf extract-Africa (GLE-A) and graviola fruit extract-Africa (GFE-A) exhibited significant cytotoxic effects on the cell proliferation in a dose-dependent manner and altered the MuD expression pattern. Cell cycle analyses revealed that GLE-A and GLE-K triggered no significant induction of apoptosis at concentrations up to 5% in U251-MG cells, while in GLE-K treated cells at 10% concentrations, there were much fewer apoptotic cells (33.64%) compared to those in GLE-A (73.55%) treated cells. In the case of GFE-A treated cells, 5% graviola extract (GE) concentration resulted in predominant cells entering the apoptotic phase (59.31%), whereas almost no significant increase in apoptotic cells was observed in GSE-A treated cells (1.38%) even up to 25% of graviola extract (GE) concentration. While using stable transfectants knock-out (KO)(−)-and overexpressing (OE)-MuD(+), significant and consistent differences in the cell viability (enhanced anti-astroglioma effect of GEs) were observed in KO-MuD(−) cells. This validated the functional consequence of MuD in the anti-astroglioma activity of GEs. Our results confirmed that GFE-A possesses the highest anti-astroglioma activity followed by the leaf extracts (GLE-A/K). This is the first report that highlights the MuD aspect of GEs.

Graviola (Annona muricate) is a coveted tropical plant that has been found to be effective against many human cancers.     

Therapeutic potential of Aurora kinase inhibitors in cancer

Aurora kinases (AKs) represent a family of serine/threonine protein kinases that regulate mitotic processes during cell division. They are primarily involved in regulating the multiple steps of mitosis, including centrosome duplication, formation of bipolar mitotic spindle, chromosome alignment on the mitotic spindle, establishment and maintenance of the spindle checkpoint and cytokinesis. As AKs are key regulators of mitosis, several studies have indicated that they have a strong association with cancer and are overexpressed in numerous cancerous cell lines as well as human malignancies. Thus, AKs represent a promising therapeutic target for anticancer drug development. In this review, the role of AKs in cancer, and the current status and therapeutic potential of AK inhibitors is discussed.     

Stuttering priapism after ingestion of alfuzosin

A patient who presented with priapism after ingestion of alfuzosin is described. He presented with recurrent priapism, which was relieved temporarily after physical exercise. It did not subside with pharmacologic management and was managed surgically using Winter's procedure. It remained quiescent for a short period, only to reappear later. After additional conservative management, he was well enough to be discharged. At 12 months of follow-up, he was well, had no penile fibrosis, was able to have unaided intercourse, and had moderately bothersome lower urinary tract symptoms. This case illustrates that no therapeutic drug is without side effects and emphasizes the need to warn patients appropriately.     

Perioperative implications of retrograde flow in both the subclavian arteries in an adult undergoing surgical repair of coarctation of aorta

During surgical repair of coarctation of aorta (CoA), management of spinal cord ischemia and prevention of paraplegia is an important issue. The risk factors for paraplegia include level and duration of aortic-clamping, clamping of left subclavian artery (SCA), intraoperative temperature, variability of collateral circulation to the spinal cord, cerebrospinal fluid pressure, upper body arterial pressure, and aortic pressure beyond the aortic clamp. A short clamp time (<30 min), and distal aortic pressure>60 mmHg, minimizes the risks of spinal cord injury. In an adult patient during surgical repair of CoA, the arterial pressure in the femoral artery remained around 45 mmHg and repair took 83 min of aortic-clamping. Neurological assessment on regaining consciousness showed no deficit of lower limbs. Aortic root angiogram had shown retrograde filling of both SCAs. A unique situation in which clamping of SCAs would increase flow to the spinal cord as their clamping would stop stealing of blood and aortic-clamping proximal to CoA will further increase collateral flow; because of these reasons, the patient tolerated prolonged aortic-clamping despite low distal aortic pressure without neurological deficit. However, aortic-clamping increased left ventricular after-load and the patient developed worsening of mitral regurgitation and pulmonary hypertension during aortic clamping.