Correlation between NT proBNP and left ventricular ejection fraction in elderly patients presenting to emergency department with dyspnoea

ObjectiveShortness of breath is a common complaint for which the elderly seek medical attention in the emergency department (ED). Differentiating cardiac from respiratory causes of dyspnoea in this population is quite a challenge. N Terminal pro brain-natriuretic-peptide (NT proBNP) has been studied extensively as a biomarker of left ventricular (LV) failure.MethodsThe NT proBNP was measured in 100 patients above 60 years of age who presented to the ED with shortness of breath. The level was compared with echocardiographic findings to assess correlation with ejection fraction (EF).ResultsThe NT proBNP values increased significantly as the functional severity of heart failure (HF) increased (P < 0.001). The mean NT proBNP level was 1503.33 pg/mL. Patients with respiratory causes of dyspnoea had a mean NT proBNP level of 309.28 pg/mL with normal LV function.ConclusionThe NT proBNP levels had a good correlation with worsening LVEF.     

Extracellular superoxide dismutase is important for hippocampal neurogenesis and preservation of cognitive functions after irradiation

Cranial irradiation is widely used in cancer therapy, but it often causes cognitive defects in cancer survivors. Oxidative stress is considered a major cause of tissue injury from irradiation. However, in an earlier study mice deficient in the antioxidant enzyme extracellular superoxide dismutase (EC-SOD KO) showed reduced sensitivity to radiation-induced defects in hippocampal functions. To further dissect the role of EC-SOD in neurogenesis and in response to irradiation, we generated a bigenic EC-SOD mouse model (OE mice) that expressed high levels of EC-SOD in mature neurons in an otherwise EC-SOD–deficient environment. EC-SOD deficiency was associated with reduced progenitor cell proliferation in the subgranular zone of dentate gyrus in KO and OE mice. However, high levels of EC-SOD in the granule cell layer supported normal maturation of newborn neurons in OE mice. Following irradiation, wild-type mice showed reduced hippocampal neurogenesis, reduced dendritic spine densities, and defects in cognitive functions. OE and KO mice, on the other hand, were largely unaffected, and the mice performed normally in neurocognitive tests. Although the resulting hippocampal-related functions were similar in OE and KO mice following cranial irradiation, molecular analyses suggested that they may be governed by different mechanisms: whereas neurotrophic factors may influence radiation responses in OE mice, dendritic maintenance may be important in the KO environment. Taken together, our data suggest that EC-SOD plays an important role in all stages of hippocampal neurogenesis and its associated cognitive functions, and that high-level EC-SOD may provide protection against irradiation-related defects in hippocampal functions.Cranial irradiation is widely used as a treatment modality for patients with primary or metastatic brain tumors (1–3), and is also used as a prophylactic treatment to prevent metastases of high-risk tumors to the nervous system (4). Although effective, cranial irradiation is associated with various complications or side effects in cancer survivors (1–3). One of the severe complications is neurocognitive impairment, which can include defects in executive functions and learning and memory (3). Neurocognitive impairments occur in both adults and children and are generally associated with higher doses and younger age (3). The pathogenesis of radiation-induced neurocognitive impairment is not completely understood, but recent studies suggest that suppressed hippocampal neurogenesis (5, 6), increased hippocampal neuronal apoptosis (7, 8), and reduced growth hormone secretion (9, 10) may be involved.The production of reactive oxygen species (ROS) is considered a major cause of radiation-induced tissue damage (11). Ionizing irradiation not only results in the acute generation of short-lived ROS, it also results in a persistent state of oxidative stress that extends up to several months or even years after irradiation (12, 13). Accordingly, animal and cell models with altered antioxidant capacities have been used to investigate the biochemical pathways involved in radiation-induced tissue and cell injuries, and experimental antioxidant-based therapies have been designed to protect normal tissues during radiation treatments (14).Hippocampal neurogenesis is important for hippocampal-dependent functions of learning and memory and the process is exquisitely sensitive to suppression by various stressors, including radiation and oxidative stress (5, 6, 15). To determine if altered redox balance in the hippocampal microenvironment affects hippocampal neurogenesis and the associated functions of learning and memory, we used a knockout mouse model (KO) deficient in the extracellular antioxidant enzyme, EC-superoxide dismutase (EC-SOD), in an earlier study with cranial irradiation (13, 16). When examined at 3–4 mo of age, EC-SOD deficiency was associated with a significant suppression of baseline neurogenesis and impaired hippocampal-dependent cognitive functions (13, 16). Unexpectedly, EC-SOD deficiency also rendered the process less sensitive to radiation-induced changes. The underlining mechanism for this paradoxical finding was not clear, but preliminary studies ruled out up-regulation of major antioxidant enzymes (13). The results suggested that the interaction between redox balance and irradiation and their effects on hippocampal functions can be complex, and understanding how these elements work in concert may be a key to identifying strategies for radioprotection.To manipulate redox balance in the hippocampus, we generated a mouse model with inducible EC-SOD transgenes (17). In the current study, we combined the inducible transgenes with EC-SOD KO and generated a bigenic mouse model, designated as the overexpressor (OE), with high levels of EC-SOD expressed only in Ca/calmodulin-dependent protein kinase- (CaMKII) positive neurons in an otherwise EC-SOD–deficient environment (17). Hippocampal neurogenesis generates new granule cells that are functionally integrated into the hippocampal network (18). Because granule cells are CaMKII-positive neurons and are the principal excitatory neurons in the dentate gyrus, the manipulation leads to an estimated four- to fivefold increase in EC-SOD activity in the hippocampal formation in OE mice (17). The OE mice were used to investigate the effects of altered EC-SOD levels at different stages of hippocampal neurogenesis and the functional consequences of learning and memory. Comparison between WT, OE, and KO mice revealed the importance of EC-SOD in progenitor cell proliferation, dendritic development, and long-term survival of newborn neurons. The study results also suggested that maintenance of the dendritic system following cranial irradiation was important for preservation of neurocognitive functions.     

A case report of cecal plasmablastic lymphoma in a HIV-negative patient

Plasmablastic lymphoma (PBL) is a unique type of diffuse proliferation of large neoplastic lymphoid cells most of which resemble B immunoblasts, but all tumor cells show the immunophenotype of plasma cells. It has a strong predilection for jaw and oral cavity in HIV-positive patients. Incidences of extraoral location of this tumor is increasingly being recognized especially in HIV-negative patients for example, stomach, jejunum, omentum, anorectum, lungs, testes, soft tissues, lymph nodes, bone marrow, skin, and central nervous system. We present a case of PBL found in cecum in an HIV-negative patient. It was accompanied by lung and lymph node involvement and presented as abdominal mass. This is only the second reported case of PBL originating in cecum.     

The Aquilegia pubiflora (Himalayan columbine) mediated synthesis of nanoceria for diverse biomedical applications

Herein, we report an eco-friendly, facile, one-pot, green synthesis of nanoceria for multiple biomedical applications. In the study, cerium oxide nanoparticles (CeO₂-NPs) were synthesized using a simple aqueous extract of Aquilegia pubiflora as an effective reducing and capping agent. The biosynthesized nanoparticles were characterized via UV-vis spectroscopy, X-ray powder diffraction (XRD), high-performance liquid chromatography (HPLC), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and Raman spectroscopy. The NPs were highly stable, exhibited high purity, and had a spherical morphology and mean size of 28 nm. FTIR and HPLC studies confirmed the successful capping of bioactive compounds on the nanoparticles. The well-characterized NPs were evaluated for a number of biomedical applications, and their antimicrobial (antifungal, antibacterial, and antileishmanial), protein kinase inhibition, anticancer, antioxidant, anti-diabetic and biocompatibility properties were studied. Our results showed that the Aquilegia pubiflora mediated CeO₂-NPs were highly active against fungal strains, compared to the tested bacterial strains, with Aspergillus niger resulting in the largest zone of inhibition (15.1 ± 0.27 mm). The particles also exhibited dose dependent leishmanicidal activity with significant LC₅₀ values toward both the amastigote (114 μg mL⁻¹) and promastigote (97 μg mL⁻¹) forms of the parasite Leishmania tropica (KWH23). The NPs were found to be moderately active against the HepG2 cell line, showing 26.78% ± 1.16% inhibition at 200 μg mL⁻¹. Last but not least, their highly biocompatible nature was observed with respect to freshly isolated human red blood cells (hRBCs), making the greenly synthesized CeO₂-NPs a novel candidates for multidimensional medical applications.

Graphical illustration of eco-friendly, facile, one-pot, green synthesis of nanoceria for multiple biomedical applications.     

Nucleoside triphosphates inhibit ADP,collagen, and epinephrine-induced platelet aggregation: Role of P2Y1 and P2Y12 receptors

Background

Platelets express two ADP receptors namely P2Y₁ and P2Y₁₂ that regulate ADP and other agonists-induced platelet aggregation. P2Y₁ receptor activation causes platelet shape change while P2Y₁₂ receptor activation induces platelet aggregation. Previously, anti-aggregatory effects of ATP on ADP-induced and pro-aggregatory effects on epinephrine-induced platelet aggregation have been reported. However, the effects of other nucleoside triphosphates on platelet aggregation have never been described. The aim of the present study was to characterise the effects of nucleoside triphosphates (ATP, UTP, GTP, and CTP) on agonist-induced platelet aggregation.

Methods

The experiments were performed on platelet rich plasma freshly isolated from blood donated by healthy human volunteers.

Results

All the nucleoside triphosphates tested inhibited ADP- and collagen-induced platelet aggregation in a concentration-dependent manner with a rank order of potency, 2MeSATP > ATP ≥ α,β,methyleneATP > UTP  >> CTP ≥ GTP. The IC₅₀ values against ADP (10 μM)-induced platelet aggregation were 0.039 ± 0.013, 18 ± 7, 25 ± 6, 32 ± 9, 360 ± 130, and 400 ± 160 μM, respectively. Low concentrations of ATP induced platelet shape change which was due to contaminating ADP. However, higher concentrations antagonised ADP and MRS2365-induced platelet shape change. The ATP analogue α,β,methyleneATP and CTP but not UTP and GTP also antagonised ADP-induced platelet shape change. Similarly, low ATP concentrations potentiated epinephrine-induced platelet aggregation that was abolished by P2Y₁ antagonist MRS2500 suggesting P2Y₁ receptor activation due to contaminating ADP. Higher ATP concentrations, α,β,methyleneATP, UTP, CTP, and GTP antagonised epinephrine-induced platelet aggregation.

Conclusion

Thus, the data demonstrate nucleoside triphosphates in general act as P2Y₁₂ receptor antagonists and antagonise ADP-, collagen-, and epinephrine-induced platelet aggregation.