RESUMO
Epilepsy is a common neurological disease worldwide, and one of its causes is genetic abnormalities. Here, we identified a point mutation in KIF4A, a member of kinesin superfamily molecular motors, in patients with neurological disorders such as epilepsy, developmental delay, and intellectual disability. KIF4 is involved in the poly (ADP-ribose) polymerase (PARP) signaling pathway, and the mutation (R728Q) strengthened its affinity with PARP1 through elongation of the KIF4 coiled-coil domain. Behavioral tests showed that KIF4-mutant mice exhibited mild developmental delay with lower seizure threshold. Further experiments revealed that the KIF4 mutation caused aberrant morphology in dendrites and spines of hippocampal pyramidal neurons through PARP1-TrkB-KCC2 pathway. Furthermore, supplementing NAD, which activates PARP1, could modulate the TrkB-KCC2 pathway and rescue the seizure susceptibility phenotype of the mutant mice. Therefore, these findings indicate that KIF4 is engaged in a fundamental mechanism regulating seizure susceptibility and could be a potential target for epilepsy treatment.
Assuntos
Epilepsia , Convulsões , Camundongos , Animais , Convulsões/genética , Transdução de Sinais , Cinesinas/genéticaRESUMO
ST-segment elevation in absence of acute coronary syndrome can be seen in multiple conditions, including acute pericarditis and coronary vasospasm, but it is rarely seen with severe hypercalcemia. The authors present a case of an 81-year-old female with a history of stage 4 squamous cell cancer of the lung, who presented to the emergency room with profound fatigue, weakness, anorexia, and drowsiness two weeks after her first chemotherapy cycle. Additionally, she had complaints of right-sided chest pain associated with worsening shortness of breath, as well as right arm numbness. An EKG obtained on arrival to the hospital showed diffuse ST-segment elevation (leads V3-V6, I, II, III, and aVF). Basic lab work found a calcium level of 20.4 mg/dl with elevated parathyroid hormone-related protein (PTHrP) of 135 pg/ml. Troponin I remained within normal limits. Serial EKS obtained during the patient's hospitalization demonstrated resolution of the ST elevation as calcium level normalized. This case emphasizes the importance of hypercalcemia as a differential diagnosis for ST-segment elevation and QT shortening when acute coronary syndrome is not present. Awareness of these EKG changes is critical for early diagnosis, recognition, and appropriate treatment.
RESUMO
A multi-centred study was designed to collect dengue epidemiologic data from government and registered private hospitals/clinics and maintained archive of frozen specimens in bio-bank to be used for future dengue epidemic control program, and assess the epidemiology of dengue fever (DF) by evaluating biochemical and oxidative status of patients. ELISA IgM antibodies test was done to confirm DF. From August 2010 to December 2011, 101 confirmed blood samples of DF patients referred to pathology lab of Jinnah Hospital Lahore were subjected to the epidemiologic assessment by evaluating the biochemical and physiological indices and alterations of circulating antioxidants. Clinical features of DF patients and effect of fever on blood components and serum proteins of liver were recorded. The hospital stay in DF, dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) showed significant difference. Significant increases in serum alanine amino transferase (ALT) (P=0.000), aspartate amino transferase (AST) (P=0.000), alkaline phosphatase (ALP) (P=0.000), malondialdehyde (MDA) along with significant decreases in total protein (TP) (P=0.000), reduced glutathione (GSH) (P=0.000), superoxide dismutase (SOD), catalase (CAT) (P=0.000), and sialic acid contents (P=0.016) were observed. A positive correlation existed between bound sialic acid levels, liver enzymes and circulating antioxidants (r=0.656, P=0.016). In the present study, alterations of circulating antioxidants in DF suggest that DF might be a metabolic response to an acute, self-limiting tropical viral infection, and a consequence of the viral inflammatory process.
