MRI-Guided Cryoablation of In-Transit Metastases from Cutaneous Melanoma: A Brief Report on a Preliminary Experience

CardioVascular and Interventional Radiology - This study aims to discuss MRI-guided cryoablation (CA) of in-transit (IT) metastases from melanoma and to retrospectively present our preliminary...     

S100B attenuates microglia activation in gliomas: possible role of STAT3 pathway

Despite significant infiltration into tumors, the effector function of macrophages (MPs) and microglia (MG) appears to be suppressed in gliomas. Although STAT3 pathway is thought to play a role in this process, the exact mechanism by which gliomas induce STAT3 activation in MPs and MG is not known. Because activation of receptor for advanced glycation end products (RAGE) can induce STAT3, and because gliomas express high levels of S100B, a RAGE ligand, we hypothesized that MP/MG STAT3 activity may be modulated through S100B-RAGE interaction. Exposure of N9 MG and bone marrow-derived monocytes (BMM) to GL261 glioma condition medium (GCM) and low (nM) levels of S100B increased RAGE expression, induced STAT3 and suppressed MG function in vitro. Furthermore, neutralization of S100B in GCM, partially reversed IL-1β suppression in BMM, suggesting that the inhibitory effect of GCM to be in part due to S100B. Finally, blockage of S100B-RAGE interaction inhibited STAT3 activation in N9 MG and in glioma MG/MP in vivo. These findings suggest that the RAGE pathway may play an important role in STAT3 induction in glioma-associated MG/MPs, and that this process may be mediated through S100B.     

TNF receptor I on human keratinocytes is a binding partner for staphylococcal protein A resulting in the activation of NF kappa B, AP-1, and downstream gene transcription

Primary human keratinocytes and immortalized HaCaT cells were analysed for their capacity to bind purified staphylococcal protein A (SpA). Co-incubation with FITC-labelled SpA led to a dose-depending attachment. Pull-down experiments with cellular extracts revealed the TNFα receptor I (TNF RI) as binding partner on keratinocytes. Thus, we next looked for expression of this receptor in human epidermis and cultured keratinocytes. TNF RI is strongly expressed on all keratinocytes analysed, both at the mRNA and protein level and activation by SpA at optimal doses of 50-100 μg/ml resulted in the phosphorylation of the TNF RI downstream kinases MEK1/2, JNK1/2, and p38 subsequently leading to translocation of the p65 NF kappa B subunit and AP-1 into the nucleus. This translocation was then followed by increased expression of IL-8 and COX-2, two known NF kappa B-induced pro-inflammatory genes. To further test the relevance of our findings, we analysed in vitro production of over 100 strains isolated from atopic eczema showing that more than 85% of the tested strains produced extracellular SpA in substantial amounts. Thus, besides superantigens, haemolysins, and other cell wall components, Staphylococcus aureus exerts pro-inflammatory stimuli on human keratinocytes through the production of SpA signalling through TNF RI.     

Melancholia in medieval Persian literature: The view of Hidayat of Al-Akhawayni

“Melancholia” seems to be the oldest term used to describe the manifestations of depression. Throughout the history of medicine, melancholia has been the focus of consideration of many scholars who have provided varying definitions of this disorder and its manifestations. This continual process has resulted in the gradual development of the concept of melancholia over time. Persian scholars were among the scientists who have studied the melancholia and contributed to its concept. One figure, Al-Akhawayni Bukhari (?-983 AD), a Persian physician whose reputation was based on the treatment of patients with mental problems, investigated this disorder. He described Melancholia and explained its clinical manifestations and treatment methods. Al-Akhawayni provided an early classification of the patients suffering from this disorder. Since the medieval Persian concept of melancholia is not well-known, this paper aims to review Al-Akhawayni’s 10^th century knowledge on melancholia which can represent the early concept of this disorder in the Near East.     

Isolated arterioportal fistula presenting with variceal hemorrhage

We report a case of life-threatening hematemesis due to portal hypertension caused by an isolated arterioportal fistula (APF). Intrahepatic APFs are extremely rare and are a cause of presinusoidal portal hypertension. Etiologies for APFs are comprised of precipitating trauma, malignancy, and hereditary hemorrhagic telangiectasia, but these were not the case in our patient. Idiopathic APFs are usually due to congenital vascular abnormalities and thus usually present in the pediatric setting. This is one of the first cases of adult-onset isolated APF who presented with portal hypertension and was successfully managed through endoscopic hemostasis and subsequent interventional radiological embolization.     

Retinitis Pigmentosa GTPase Regulator (RPGR) protein isoforms in mammalian retina: insights into X-linked Retinitis Pigmentosa and associated ciliopathies

Mutations in the cilia-centrosomal protein Retinitis Pigmentosa GTPase Regulator (RPGR) are a frequent cause of retinal degeneration. The RPGR gene undergoes complex alternative splicing and encodes multiple protein isoforms. To elucidate the function of major RPGR isoforms (RPGR 1-19 and RPGR ORF15), we have generated isoform-specific antibodies and examined their expression and localization in the retina. Using sucrose-gradient centrifugation, immunofluorescence and co-immunoprecipitation methods, we show that RPGR isoforms localize to distinct sub-cellular compartments in mammalian photoreceptors and associate with a number of cilia-centrosomal proteins. The RCC1-like domain of RPGR, which is present in all major RPGR isoforms, is sufficient to target it to the cilia and centrosomes in cultured cells. Our findings indicate that multiple isotypes of RPGR may perform overlapping yet somewhat distinct transport-related functions in photoreceptors.     

The Quality of Life of Patients with Malignant Gliomas and Their Caregivers

ABSTRACT

The grim prognosis that accompanies a diagnosis of a malignant glioma affects quality of life (QOL) as patients attempt to adapt to overwhelming losses. Caregivers also experience negative changes in QOL as responsibilities grow. This pilot study measured the QOL of patients with malignant gliomas prior to tumor progression and the QOL of their caregivers. It examined negative and positive factors that impacted the QOL while highlighting positive factors often overlooked in brain tumor QOL research. Standardized QOL questionnaires and focus groups were utilized. Patients experienced distress in the domains of physical, psychological, and social QOL but in all four of the QOL domains there were also positive outcomes. Caregiver data demonstrated mostly positive outcomes in the four QOL domains except for loved one's declining health and fear that the loved one would die.     

The effect of ultrasound on the expression of CNTF gene, a possible cause of ultrasound influence on the rate of injured peripheral nerve regeneration

In this article we evaluate the effects of ultrasound radiation and its causes on the rate of injured peripheral nerve regeneration by crushing the sciatic nerve of rats with hemostatic forceps. The rats were divided into three test and one control groups. The test groups were radiated using three different types of ultrasound parameters while the control group just received sham expose. The amount of nerve regeneration was measured via functional test by extracting sciatic functional index from rats paw prints. The results showed that one of the test group parameters had the best functional results compared to other groups. Obtaining this outcome, the investigations continued by 50 rats with crushed sciatic nerve. These rats again divided into two test and control groups while for the test group the best parameters were assigned. In different time intervals compound muscle action potential wave was recorded from five rats of each group. Then their sciatic nerves were extracted to measure the amount of ciliary neurotropic factor gene expression by real time polymerase chain reaction. Crush injury sets the sciatic functional index to about ?90 and compound muscle action potential to 6.8 mV in both control and test groups. After the period of treatment with ultrasound, the sciatic functional index reached the value of ?25 in control group and ?10 in test group and compound muscle action potential value reached 11 in control and 18 in test group. The results of electrophysiological tests confirmed the results of functional tests. At the end of the second, third and fourth weeks, the outcomes of real time polymerase chain reaction showed that the expression of ciliary neurotropic factor gene in test group was higher than control group as well as the amount in test group was approximately 11, 2 and 6 times higher than test group in corresponding weeks. Hence we can conclude that increase in the expression of ciliary neurotropic factor gene, as a nerve growth factor, following ultrasound radiation, can be considered as the reason of the effect of ultrasound on the rate of injured nerve regeneration.