Pharmacological Aspects of Vipera xantina palestinae Venom

In Israel, Vipera xantina palestinae (V.x.p.) is the most common venomous snake, accounting for several hundred cases of envenomation in humans and domestic animals every year, with a mortality rate of 0.5 to 2%. In this review we will briefly address the research developments relevant to our present understanding of the structure and function of V.x.p. venom with emphasis on venom disintegrins. Venom proteomics indicated the presence of four families of pharmacologically active compounds: (i) neurotoxins; (ii) hemorrhagins; (iii) angioneurin growth factors; and (iv) different types of integrin inhibitors. Viperistatin, a α1β1selective KTS disintegrin and VP12, a α2β1 selective C-type lectin were discovered. These snake venom proteins represent promising tools for research and development of novel collagen receptor selective drugs. These discoveries are also relevant for future improvement of antivenom therapy towards V.x.p. envenomation

Human Umbilical Cord Blood Stem Cells: Rational for Use as a Neuroprotectant in Ischemic Brain Disease

The use of stem cells for reparative medicine was first proposed more than three decades ago. Hematopoietic stem cells from bone marrow, peripheral blood and human umbilical cord blood (CB) have gained major use for treatment of hematological indications. CB, however, is also a source of cells capable of differentiating into various non-hematopoietic cell types, including neural cells. Several animal model reports have shown that CB cells may be used for treatment of neurological injuries. This review summarizes the information available on the origin of CB-derived neuronal cells and the mechanisms proposed to explain their action. The potential use of stem/progenitor cells for treatment of ischemic brain injuries is discussed. Issues that remain to be resolved at the present stage of preclinical trials are addressed

Blended learning in nursing pharmacology: elevating cognitive skills, engagement and academic outcomes

Pharmacological education is crucial for healthcare professionals to safely manage medications and reduce errors. Traditional lecture-based learning (LBL) often struggles to address this complexity, whereas newer methods, such as flipped classrooms and problem-based learning, yield mixed results, particularly in pre-clinical contexts, owing to students’ limited experience. Our nursing pharmacology course under LBL recorded a high failure rate of 37.8% and marginal passing scores across five cohorts (n = 849 students). An analysis using Bloom’s taxonomy revealed significant gaps in higher-order cognitive skills. As a remedy, the course was transformed into a novel blended learning format that integrated question-based learning (QBL) to enhance critical thinking across all cognitive levels. This model blends asynchronous and synchronous learning, is tailored to individual needs in large classes, and fosters continuous, student-centric learning. The redesign markedly decreased the failure rate by approximately 2.8-fold and increased the average grade by 11.8 points among 426 students. It notably improved the pass rates in advanced cognitive categories, such as “Evaluate” and “Create” by 19.0% and 24.2%, respectively. Additionally, the blended course showed increased student engagement, reflecting a dynamic and effective learning environment that significantly elevated participation and academic outcomes at all cognitive levels. This study demonstrated the profound impact of blended learning in pharmacology. By integrating QBL with various teaching methods, it surpasses traditional lecture-based limitations, enhancing engagement and understanding of complex topics by nursing students. Notable improvements in foundational and advanced learning suggest its broader application in health professionals’ education, effectively equipping students for clinical pharmacology challenges

Image1_Blended learning in nursing pharmacology: elevating cognitive skills, engagement and academic outcomes.pdf

Pharmacological education is crucial for healthcare professionals to safely manage medications and reduce errors. Traditional lecture-based learning (LBL) often struggles to address this complexity, whereas newer methods, such as flipped classrooms and problem-based learning, yield mixed results, particularly in pre-clinical contexts, owing to students’ limited experience. Our nursing pharmacology course under LBL recorded a high failure rate of 37.8% and marginal passing scores across five cohorts (n = 849 students). An analysis using Bloom’s taxonomy revealed significant gaps in higher-order cognitive skills. As a remedy, the course was transformed into a novel blended learning format that integrated question-based learning (QBL) to enhance critical thinking across all cognitive levels. This model blends asynchronous and synchronous learning, is tailored to individual needs in large classes, and fosters continuous, student-centric learning. The redesign markedly decreased the failure rate by approximately 2.8-fold and increased the average grade by 11.8 points among 426 students. It notably improved the pass rates in advanced cognitive categories, such as “Evaluate” and “Create” by 19.0% and 24.2%, respectively. Additionally, the blended course showed increased student engagement, reflecting a dynamic and effective learning environment that significantly elevated participation and academic outcomes at all cognitive levels. This study demonstrated the profound impact of blended learning in pharmacology. By integrating QBL with various teaching methods, it surpasses traditional lecture-based limitations, enhancing engagement and understanding of complex topics by nursing students. Notable improvements in foundational and advanced learning suggest its broader application in health professionals’ education, effectively equipping students for clinical pharmacology challenges.</p

Table1_Blended learning in nursing pharmacology: elevating cognitive skills, engagement and academic outcomes.pdf

Pharmacological education is crucial for healthcare professionals to safely manage medications and reduce errors. Traditional lecture-based learning (LBL) often struggles to address this complexity, whereas newer methods, such as flipped classrooms and problem-based learning, yield mixed results, particularly in pre-clinical contexts, owing to students’ limited experience. Our nursing pharmacology course under LBL recorded a high failure rate of 37.8% and marginal passing scores across five cohorts (n = 849 students). An analysis using Bloom’s taxonomy revealed significant gaps in higher-order cognitive skills. As a remedy, the course was transformed into a novel blended learning format that integrated question-based learning (QBL) to enhance critical thinking across all cognitive levels. This model blends asynchronous and synchronous learning, is tailored to individual needs in large classes, and fosters continuous, student-centric learning. The redesign markedly decreased the failure rate by approximately 2.8-fold and increased the average grade by 11.8 points among 426 students. It notably improved the pass rates in advanced cognitive categories, such as “Evaluate” and “Create” by 19.0% and 24.2%, respectively. Additionally, the blended course showed increased student engagement, reflecting a dynamic and effective learning environment that significantly elevated participation and academic outcomes at all cognitive levels. This study demonstrated the profound impact of blended learning in pharmacology. By integrating QBL with various teaching methods, it surpasses traditional lecture-based limitations, enhancing engagement and understanding of complex topics by nursing students. Notable improvements in foundational and advanced learning suggest its broader application in health professionals’ education, effectively equipping students for clinical pharmacology challenges.</p

Bio-imaging of colorectal cancer models using near infrared labeled epidermal growth factor.

Novel strategies that target the epidermal growth factor receptor (EGFR) have led to the clinical development of monoclonal antibodies, which treat metastatic colorectal cancer (mCRC) but only subgroups of patients with increased wild type KRAS and EGFR gene copy, respond to these agents. Furthermore, resistance to EGFR blockade inevitably occurred, making future therapy difficult. Novel bio-imaging (BOI) methods may assist in quantization of EGFR in mCRC tissue thus complementing the immunohistochemistry methodology, in guiding the future treatment of these patients. The aim of the present study was to explore the usefulness of near infrared-labeled EGF (EGF-NIR) for bio-imaging of CRC using in vitro and in vivo orthotopic tumor CRC models and ex vivo human CRC tissues. We describe the preparation and characterization of EGF-NIR and investigate binding, using BOI of a panel of CRC cell culture models resembling heterogeneity of human CRC tissues. EGF-NIR was specifically and selectively bound by EGFR expressing CRC cells, the intensity of EGF-NIR signal to background ratio (SBR) reflected EGFR levels, dose-response and time course imaging experiments provided optimal conditions for quantization of EGFR levels by BOI. EGF-NIR imaging of mice with HT-29 orthotopic CRC tumor indicated that EGF-NIR is more slowly cleared from the tumor and the highest SBR between tumor and normal adjacent tissue was achieved two days post-injection. Furthermore, images of dissected tissues demonstrated accumulation of EGF-NIR in the tumor and liver. EGF-NIR specifically and strongly labeled EGFR positive human CRC tissues while adjacent CRC tissue and EGFR negative tissues expressed weak NIR signals. This study emphasizes the use of EGF-NIR for preclinical studies. Combined with other methods, EGF-NIR could provide an additional bio-imaging specific tool in the standardization of measurements of EGFR expression in CRC tissues

Human Umbilical Cord Blood Stem Cells: Rational for Use as a Neuroprotectant in Ischemic Brain Disease

The use of stem cells for reparative medicine was first proposed more than three decades ago. Hematopoietic stem cells from bone marrow, peripheral blood and human umbilical cord blood (CB) have gained major use for treatment of hematological indications. CB, however, is also a source of cells capable of differentiating into various non-hematopoietic cell types, including neural cells. Several animal model reports have shown that CB cells may be used for treatment of neurological injuries. This review summarizes the information available on the origin of CB-derived neuronal cells and the mechanisms proposed to explain their action. The potential use of stem/progenitor cells for treatment of ischemic brain injuries is discussed. Issues that remain to be resolved at the present stage of preclinical trials are addressed

α-Synuclein-induced Kv4 channelopathy in mouse vagal motoneurons causes non-motor parkinsonian symptoms

No disease modifying therapy is currently available for Parkinson’s disease (PD), the second most common neurodegenerative disease. The long non-motor prodromal phase of PD is a window of opportunity for early detection and intervention. However, we lack the pathophysiological understanding to develop selective biomarkers and interventions. By developing a mutant α-synuclein selective-overexpression mouse model of prodromal PD, we identified a cell-autonomous selective Kv4 channelopathy in dorsal motor nucleus of the vagus (DMV) neurons. This functional remodeling of intact DMV neurons leads to impaired pacemaker function in vitro and in vivo, which in turn reduces gastrointestinal motility which is a common, very early symptom of prodromal PD. We show for the first time a causal chain of events from α-synuclein via a biophysical dysfunction of specific neuronal populations to a clinically relevant prodromal symptom. These findings can facilitate the rational design of clinical biomarkers to identify people at risk for PD

Spectral intensity maps of BOI images of specific EGF-NIR binding in human CRC tissues.

<p>Images of five typical slices, specifically labeled with EGF-NIR, as described in legend for Fig. 7. The 800 nm Odyssey Infrared Imager acquired images were processed using applied spectral imaging software, Spectral View. Intensity scale-red-brown (5) high expression of EGF-NIR binding; green (4) intermediate expression; blue (3) very low expression.</p

Whole body <i>in vivo</i> and isolated tissue <i>ex vivo</i> EGF-NIR BOI of mice with HT-29 orthotopic tumors.

<p>(A) Photograph of an orthotopic tumor and EGFR protein expression in the tumors; (B) Time course of EGF-NIR accumulation in tissues of tumor-bearing mice. The mice were injected i.v. with 1 nmol of EGF-NIR in untreated mice (upper row, n = 6) or mice pre-injected with 1 µg/ml cetuximab (lower row, n = 4); high resolution BOI of a mouse injected with EGF-NIR and circles indicate ROI measurements (C) Time course of tissue accumulation of EGF-NIR at 48 hours from mice presented in B; Signal intensity at 800 nm were normalized to background fluorescence using an arbitrary tumor circle (10–20 ROIs/mouse) compared to an identical area on the flank (adjacent muscle); * p<0.05 compared to EGF-NIR 4 hours; ** p<0.05 compared to mice injected with EGF-NIR; (D) EGF-NIR signal/background ratio in isolated tissue from the tumor-bearing mice 48 hours after injection. * p<0.05 compared to muscle, ** p<0.05 compared to liver; Insert: Upper-photographs of tissues in the dish; Middle-NIR images; Lower-spectral intensity maps; Intensity scale-red-brown (5) high expression; blue (3) very low expression.</p