Endometrial Cancer Presenting as Acute Urinary Retention: a Case Report and Review of the Literature

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Endometrial Cancer Presenting as Acute Urinary Retention : a Case Report and Review of The Literature

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Extracellular electrical signals in a neuron-surface junction: model of heterogeneous membrane conductivity

Signals recorded from neurons with extracellular planar sensors have a wide range of waveforms and amplitudes. This variety is a result of different physical conditions affecting the ion currents through a cellular membrane. The transmembrane currents are often considered by macroscopic membrane models as essentially a homogeneous process. However, this assumption is doubtful, since ions move through ion channels, which are scattered within the membrane. Accounting for this fact, the present work proposes a theoretical model of heterogeneous membrane conductivity. The model is based on the hypothesis that both potential and charge are distributed inhomogeneously on the membrane surface, concentrated near channel pores, as the direct consequence of the inhomogeneous transmembrane current. A system of continuity equations having non-stationary and quasi-stationary forms expresses this fact mathematically. The present work performs mathematical analysis of the proposed equations, following by the synthesis of the equivalent electric element of a heterogeneous membrane current. This element is further used to construct a model of the cell-surface electric junction in a form of the equivalent electrical circuit. After that a study of how the heterogeneous membrane conductivity affects parameters of the extracellular electrical signal is performed. As the result it was found that variation of the passive characteristics of the cell-surface junction, conductivity of the cleft and the cleft height, could lead to different shapes of the extracellular signals

Anticancer Gene Transfer for Cancer Gene Therapy

Gene therapy vectors are among the treatments currently used to treat malignant tumors. Gene therapy vectors use a specific therapeutic transgene that causes death in cancer cells. In early attempts at gene therapy, therapeutic transgenes were driven by non-specific vectors which induced toxicity to normal cells in addition to the cancer cells. Recently, novel cancer specific viral vectors have been developed that target cancer cells leaving normal cells unharmed. Here we review such cancer specific gene therapy systems currently used in the treatment of cancer and discuss the major challenges and future directions in this field

Abortive Autophagy Induces Endoplasmic Reticulum Stress and Cell Death in Cancer Cells

Autophagic cell death or abortive autophagy has been proposed to eliminate damaged as well as cancer cells, but there remains a critical gap in our knowledge in how this process is regulated. The goal of this study was to identify modulators of the autophagic cell death pathway and elucidate their effects on cellular signaling and function. The result of our siRNA library screenings show that an intact coatomer complex I (COPI) is obligatory for productive autophagy. Depletion of COPI complex members decreased cell survival and impaired productive autophagy which preceded endoplasmic reticulum stress. Further, abortive autophagy provoked by COPI depletion significantly altered growth factor signaling in multiple cancer cell lines. Finally, we show that COPI complex members are overexpressed in an array of cancer cell lines and several types of cancer tissues as compared to normal cell lines or tissues. In cancer tissues, overexpression of COPI members is associated with poor prognosis. Our results demonstrate that the coatomer complex is essential for productive autophagy and cellular survival, and thus inhibition of COPI members may promote cell death of cancer cells when apoptosis is compromised

Redox regulation of mitochondrial fission, protein misfolding, synaptic damage, and neuronal cell death: potential implications for Alzheimer’s and Parkinson’s diseases

Normal mitochondrial dynamics consist of fission and fusion events giving rise to new mitochondria, a process termed mitochondrial biogenesis. However, several neurodegenerative disorders manifest aberrant mitochondrial dynamics, resulting in morphological abnormalities often associated with deficits in mitochondrial mobility and cell bioenergetics. Rarely, dysfunctional mitochondrial occur in a familial pattern due to genetic mutations, but much more commonly patients manifest sporadic forms of mitochondrial disability presumably related to a complex set of interactions of multiple genes (or their products) with environmental factors (G × E). Recent studies have shown that generation of excessive nitric oxide (NO), in part due to generation of oligomers of amyloid-β (Aβ) protein or overactivity of the NMDA-subtype of glutamate receptor, can augment mitochondrial fission, leading to frank fragmentation of the mitochondria. S-Nitrosylation, a covalent redox reaction of NO with specific protein thiol groups, represents one mechanism contributing to NO-induced mitochondrial fragmentation, bioenergetic failure, synaptic damage, and eventually neuronal apoptosis. Here, we summarize our evidence in Alzheimer’s disease (AD) patients and animal models showing that NO contributes to mitochondrial fragmentation via S-nitrosylation of dynamin-related protein 1 (Drp1), a protein involved in mitochondrial fission. These findings may provide a new target for drug development in AD. Additionally, we review emerging evidence that redox reactions triggered by excessive levels of NO can contribute to protein misfolding, the hallmark of a number of neurodegenerative disorders, including AD and Parkinson’s disease. For example, S-nitrosylation of parkin disrupts its E3 ubiquitin ligase activity, and thereby affects Lewy body formation and neuronal cell death

"I think my body has become addicted to those tablets" Chronic heart failure patients' understanding of and beliefs about their illness and its treatment: a qualitative longitudinal study from Uganda

Patients with heart failure in Uganda present for health care with advanced structural heart disease, have repeated hospitalizations and poorly controlled disease symptoms. The reasons for these are unclear. Literature from other settings shows that patients' understanding of their illness and their beliefs influence their health related behaviour. The study aimed to explore the beliefs of patients with heart failure, their understanding of their illness and its treatment, and how this influenced their health related behaviour to inform future health education programs, information and palliative care services.Serial qualitative in-depth interviews were conducted with Heart Failure patients who were purposively sampled and recruited in Mulago National Referral Hospital until thematic saturation was reached. In-depth interviews were conducted at three time points over the course of their illness with intervals of 3 months between interviews. A grounded theory approach was used in data analysis. The University of Edinburgh ethics committee, Mulago Hospital Research Ethics committee and the Uganda National Council of Science and Technology (Reference numbers D/GC/178; MREC 33, SS 3083 respectively) approved the research.A total of 40 face to face qualitative longitudinal interviews (36-patient alone, 4 paired-patient and family carer), were conducted with 21 patients. The findings revealed that heart failure patients were unaware of the symptoms of the illness and their definition of illness differed from that of health professionals. Patients understood their diagnosis, cause of illness, prognosis and the importance of the medicines differently from health professionals, and had insufficient information on self-care. Lay beliefs were used to explain many aspects of the illness and treatments. All these influenced where patients sought care and their adherence to treatment, self-care and follow up leading to uncontrolled disease.There is a high level of health illiteracy among heart failure patients in Uganda. Patients rely on lay beliefs to make health decisions and medical information is often miscomprehended. There is an urgent need for health education using culturally appropriate information