Dopaminergic modulation of transcallosal activity of cat motor cortical neurons

The effects of dopamine (DA) and its antagonists on the transcallosal activity of pyramidal tract neurons (PTNs) and non-PTNs in the anesthetized cat motor cortex were studied with iontophoretic applications; dopamine, SCH 23390 (D1 antagonist), sulpiride (D2 antagonist) and haloperidol. Neuronal activity was recorded with a multi-barreled glass microelectrode. Transcallosal neuronal activity was evoked by stimulation of the contralateral motor cortex. The number of spikes thus activated was counted for the control and test conditions after application of each drug: (1) dopamine application decreased the number of spikes evoked by transcallosal stimulation; (2) application of SCH 23390, sulpiride and haloperidol restored these decreased spike numbers to the control level; (3) latency of neuronal response to transcallosal stimulation was not affected by the application of either DA, SCH 23390, sulpiride or haloperidol; and (4) there was no significant difference between PTNs and non-PTNs in the manner of response to DA and its antagonist applications. Our conclusion is that dopamine modulated the transcallosal neuronal response in the cat motor cortex in a suppressive manner. This fact suggested that interhemispheric neuronal communications could be subjected to suppressive modification by the dopaminergic system.     

Effective doses to patients undergoing thoracic computed tomography examinations

The purpose of this study was to investigate how x-ray technique factors and effective doses vary with patient size in chest CT examinations. Technique factors (kVp, mAs, section thickness, and number of sections) were recorded for 44 patients who underwent a routine chest CT examination. Patient weights were recorded together with dimensions and mean Hounsfield unit values obtained from representative axial CT images. The total mass of directly irradiated patient was modeled as a cylinder of water to permit the computation of the mean patient dose and total energy imparted for each chest CT examination. Computed values of energy imparted during the chest CT examination were converted into effective doses taking into account the patient weight. Patient weights ranged from 4.5 to 127 kg, and half the patients in this study were children under 18 years of age. All scans were performed at 120 kVp with a 1 s scan time. The selected tube current showed no correlation with patient weight (r2=0.06), indicating that chest CT examination protocols do not take into account for the size of the patient. Energy imparted increased with increasing patient weight, with values of energy imparted for 10 and 70 kg patients being 85 and 310 mJ, respectively. The effective dose showed an inverse correlation with increasing patient weight, however, with values of effective dose for 10 and 70 kg patients being 9.6 and 5.4 mSv, respectively. Current CT technique factors (kVp/mAs) used to perform chest CT examinations result in relatively high patient doses, which could be reduced by adjusting technique factors based on patient size.     

Dangerous liaisons: complement,coagulation, and kallikrein/kinin cross-talk act as a linchpin in the events leading to thromboinflammation

Innate immunity is fundamental to our defense against microorganisms. Physiologically, the intravascular innate immune system acts as a purging system that identifies and removes foreign substances leading to thromboinflammatory responses, tissue remodeling, and repair. It is also a key contributor to the adverse effects observed in many diseases and therapies involving biomaterials and therapeutic cells/organs. The intravascular innate immune system consists of the cascade systems of the blood (the complement, contact, coagulation, and fibrinolytic systems), the blood cells (polymorphonuclear cells, monocytes, platelets), and the endothelial cell lining of the vessels. Activation of the intravascular innate immune system in vivo leads to thromboinflammation that can be activated by several of the system's pathways and that initiates repair after tissue damage and leads to adverse reactions in several disorders and treatment modalities. In this review, we summarize the current knowledge in the field and discuss the obstacles that exist in order to study the cross-talk between the components of the intravascular innate immune system. These include the use of purified in vitro systems, animal models and various types of anticoagulants. In order to avoid some of these obstacles we have developed specialized human whole blood models that allow investigation of the cross-talk between the various cascade systems and the blood cells. We in particular stress that platelets are involved in these interactions and that the lectin pathway of the complement system is an emerging part of innate immunity that interacts with the contact/coagulation system. Understanding the resulting thromboinflammation will allow development of new therapeutic modalities.     

Preferential production of IgG1, IL-4 and IL-10 in MuSK-immunized mice

Myasthenia gravis (MG) is an autoimmune disease characterized by muscle weakness associated with acetylcholine receptor (AChR), muscle-specific receptor kinase (MuSK) or low-density lipoprotein receptor-related protein 4 (LRP4)-antibodies. MuSK-antibodies are predominantly of the non-complement fixing IgG4 isotype. The MuSK associated experimental autoimmune myasthenia gravis (EAMG) model was established in mice to investigate immunoglobulin (Ig) and cytokine responses related with MuSK immunity. C57BL/6 (B6) mice immunized with 30 μg of recombinant human MuSK in incomplete or complete Freund's adjuvant (CFA) showed significant EAMG susceptibility (> 80% incidence). Although mice immunized with 10 μg of MuSK had lower EAMG incidence (14.3%), serum MuSK-antibody levels were comparable to mice immunized with 30 μg MuSK. While MuSK immunization stimulated production of all antibody isotypes, non-complement fixing IgG1 was the dominant anti-MuSK Ig isotype in both sera and neuromuscular junctions. Moreover, MuSK immunized IgG1 knockout mice showed very low serum MuSK-antibody levels. Sera and MuSK-stimulated lymph node cell supernatants of MuSK immunized mice showed significantly higher levels of IL-4 and IL-10 (but not IFN-γ and IL-12), than those of CFA immunized mice. Our results suggest that through activation of Th2-type cells, anti-MuSK immunity promotes production of IL-4, which in turn activates anti-MuSK IgG1, the mouse analog of human IgG4. These findings might provide clues for the pathogenesis of other IgG4-related diseases as well as development of disease specific treatment methods (e.g. specific IgG4 inhibitors) for MuSK-related MG.     

Characterization of the Zebrafish atxn1/axh Gene Family

In mammals, ataxin-1 (ATXN1) is a member of a family of proteins in which each member contains an AXH domain. Expansion of the polyglutamine tract in ATXN1 causes the neurodegenerative disease, spinocerebellar ataxia type 1 (SCA1) with prominent cerebellar pathology. Toward a further characterization of the genetic diversification of the ATXN1/AXH gene family, we identified and characterized members of this gene family in zebrafish, a lower vertebrate with a cerebellum. The zebrafish genome encodes two ATXN1 homologs, atxn1a and atxn1b, and one ATXN1L homolog, atxn1l. Key biochemical features of the human ATXN1 protein not seen in the invertebrate homologs (a nuclear localization sequence and a site of phosphorylation at serine 776) are conserved in the zebrafish homologs, and all three zebrafish Atxn1/Axh proteins behave similarly to their human counterparts in tissue-culture cells. Importantly, each of the three homologs is expressed in the zebrafish cerebellum, which in humans, is a prominent site of SCA1 pathogenesis. In addition, atxn1a and atxn1b are expressed in the developing zebrafish cerebellum. These data show that in zebrafish, a lower vertebrate, the complexity of the atxn1/axh gene family is more similar to higher vertebrates than invertebrates with a simple central nervous system and suggests a relationship between the diversification of the ATXN1/AXH gene family and the development of a complex central nervous system, including a cerebellum.     

Cocaine interacts with the novelty-seeking trait to modulate FGFR1 gene expression in the rat

The present study sought to determine the interaction between the novelty-seeking trait and cocaine treatment on gene expression in the fibroblast growth factor (FGF) system. Specifically, we assessed the regulation of FGFR1 in response to cocaine in animals that were selectively bred on the basis of their locomotor response to a novel environment. High-responder (HR) rats are those that exhibit increased locomotor response and exploratory behavior in a novel environment and low-responder (LR) rats are those that exhibit lower levels of exploratory behavior and are less active. Both phenotypes received daily injections of either cocaine (15 mg/kg, i.p.) or saline for 7 consecutive days. Animals were sacrificed 45 min following their last injection and FGFR1 gene expression was assessed in the hippocampus and prefrontal cortex by mRNA in situ hybridization. HR-bred rats exhibited increased FGFR1 mRNA in the hippocampus compared to LR-bred rats. Furthermore, cocaine decreased FGFR1 mRNA in the hippocampus and increased FGFR1 mRNA in the prefrontal cortex. Finally, HR and LR rats differed in their response to cocaine between brain regions. In the hippocampus, cocaine decreased gene expression in HR-bred rats without affecting LR-bred rats, whereas in the prefrontal cortex cocaine increased gene expression in LR-bred rats without affecting HR-bred rats. These results suggest that cocaine interacts with the novelty-seeking trait to alter gene expression. Thus, the FGF system may contribute to individual differences in the response to drugs of abuse.     

Flexible chitin films as potential wound-dressing materials: wound model studies

Chitin films possessing increased flexibility, softness, transparency, and conformability have been prepared. These attributes enable the potential application of chitin films as occlusive, semipermeable film wound dressings similar to commercial products such as Opsite trade mark. The chitin films are generally nonabsorbent, exhibiting a total weight gain of only up to 120-160% in physiological fluid. Dry chitin films transpire water vapor at a rate of about 600 g/m(2)/24 h, similar to commercial polyurethane-based film dressings, but rises to 2400 g/m(2)/24 h, when wet, which is higher than the water vapor transmission rate of intact skin. The chitin films are nontoxic to human skin fibroblasts, maintaining 70-80% cell viability. Wound studies using a rat model showed no signs of allergenicity or the high inflammatory response associated with biodegradable biomaterials. The chitin films displayed accelerated wound-healing properties. Based on histological examination, wound sites dressed with the chitin films stabilized and healed faster, and appeared stronger than those dressed with Opsite trade mark and gauze dressings after 7 days of healing.     

SARS-CoV-2 and dengue virus co-infection: Epidemiology,pathogenesis, diagnosis,treatment, and management

SARS-CoV-2 and dengue virus co-infection cases have been on the rise in dengue-endemic regions as coronavirus disease 2019 (COVID-19) spreads over the world, posing a threat of a co-epidemic. The risk of comorbidity in co-infection cases is greater than that of a single viral infection, which is a cause of concern. Although the pathophysiologies of the two infections are different, the viruses have comparable effects within the body, resulting in identical clinical symptoms in the case of co-infection, which adds to the complexity. Overlapping symptoms and laboratory features make proper differentiation of the infections important. However, specific biomarkers provide precise results that can be utilised to diagnose and treat a co-infection, whether it is simply COVID-19, dengue, or a co-infection. Though their treatment is distinguished, it becomes more complicated in circumstances of co-infection. As a result, regardless of whatever infection the first symptom points to, confirmation diagnosis of both COVID-19 and dengue should be mandatory, particularly in dengue-endemic regions, to prevent health deterioration in individuals treated for a single infection. There is still a scarcity of concise literature on the epidemiology, pathophysiology, diagnosis, therapy, and management of SARS-CoV-2 and dengue virus co-infection. The epidemiology of SARS-CoV-2 and dengue virus co-infection, the mechanism of pathogenesis, and the potential impact on patients are summarised in this review. The possible diagnosis with biomarkers, treatment, and management of the SARS-CoV-2 and dengue viruses are also discussed. This review will shed light on the appropriate diagnosis, treatment, and management of the patients suffering from SARS-CoV-2 and dengue virus co-infection.