Hypersensitivity vasculitis induced by cefoperazone/sulbactam

Background

Cefoperazone has not been reported to cause vasculitic complications before. Here, we report a case of hypersensitivity vasculitis associated with cefoperazone/sulbactam.

Case presentation

A 13-year-old girl with appendicitis developed hypersensitivity vasculitis on the fifth day of cefoperazone/sulbactam therapy. Hypersensitivity vasculitis resolved gradually after removal of the agent on the seventh day and did not recur. Although hypersensitivity vasculitis has multiple causes, coexistence of hypersensitivity vasculitis and cefoperazone treatment, and the quite resolution of the disease after removal of the drug, strongly favours a causative relationship.

Conclusion

To our knowledge, this is the first report of a hypersensitivity vasculitis associated with cefoperazone.     

Efficient Isolation of Pure and Functional Mitochondria from Mouse Tissues Using Automated Tissue Disruption and Enrichment with Anti-TOM22 Magnetic Beads

To better understand molecular mechanisms regulating changes in metabolism, as observed e.g. in diabetes or neuronal disorders, the function of mitochondria needs to be precisely determined. The usual isolation methods such as differential centrifugation result in isolates of highly variable quality and quantity. To fulfill the need of a reproducible isolation method from solid tissues, which is suitable to handle parallel samples simultaneously, we developed a protocol based on anti-TOM22 (translocase of outer mitochondrial membrane 22 homolog) antibody-coupled magnetic beads. To measure oxygen consumption rate in isolated mitochondria from various mouse tissues, a traditional Clark electrode and the high-throughput XF Extracellular Flux Analyzer were used. Furthermore, Western blots, transmission electron microscopic and proteomic studies were performed to analyze the purity and integrity of the mitochondrial preparations. Mitochondrial fractions isolated from liver, brain and skeletal muscle by anti-TOM22 magnetic beads showed oxygen consumption capacities comparable to previously reported values and little contamination with other organelles. The purity and quality of isolated mitochondria using anti-TOM22 magnetic beads was compared to traditional differential centrifugation protocol in liver and the results indicated an obvious advantage of the magnetic beads method compared to the traditional differential centrifugation technique.     

Whole-mtDNA genome sequence analysis of ancient African lineages

Studies of human mitochondrial (mt) DNA genomes demonstrate that the root of the human phylogenetic tree occurs in Africa. Although 2 mtDNA lineages with an African origin (haplogroups M and N) were the progenitors of all non-African haplogroups, macrohaplogroup L (including haplogroups L0-L6) is limited to sub-Saharan Africa. Several L haplogroup lineages occur most frequently in eastern Africa (e.g., L0a, L0f, L5, and L3g), but some are specific to certain ethnic groups, such as haplogroup lineages L0d and L0k that previously have been found nearly exclusively among southern African "click" speakers. Few studies have included multiple mtDNA genome samples belonging to haplogroups that occur in eastern and southern Africa but are rare or absent elsewhere. This lack of sampling in eastern Africa makes it difficult to infer relationships among mtDNA haplogroups or to examine events that occurred early in human history. We sequenced 62 complete mtDNA genomes of ethnically diverse Tanzanians, southern African Khoisan speakers, and Bakola Pygmies and compared them with a global pool of 226 mtDNA genomes. From these, we infer phylogenetic relationships amongst mtDNA haplogroups and estimate the time to most recent common ancestor (TMRCA) for haplogroup lineages. These data suggest that Tanzanians have high genetic diversity and possess ancient mtDNA haplogroups, some of which are either rare (L0d and L5) or absent (L0f) in other regions of Africa. We propose that a large and diverse human population has persisted in eastern Africa and that eastern Africa may have been an ancient source of dispersion of modern humans both within and outside of Africa.     

Endothelins: regulators of extracellular matrix protein production in diabetes

Fibronectin (FN), a key extracellular matrix protein, is upregulated in target organs of diabetic angiopathy and in cultured cells exposed to high levels of glucose. FN has also been reported to undergo alternative splicing to produce the extra domain-B (ED-B) containing isoform, which is exclusively expressed during embryogenesis, tissue repair, and tumoral angiogenesis. The present study was aimed at elucidating the role and mechanism of endothelins (ETs) in FN and ED-B FN expression in diabetes. We investigated vitreous samples for ED-B FN expression from patients undergoing vitrectomy for proliferative diabetic retinopathy. Our results show increased FN and ED-B FN expression in the vitreous of diabetic patients in association with augmented ET-1. Using an antibody specific to the ED-B segment of FN, we show an increase in serum ED-B FN levels in patients with diabetic retinopathy and nephropathy. We further examined retinal tissues, as well as renal and cardiac tissues, from streptozotocin-induced diabetic rats. Diabetes increased FN and ED-B FN in all three organs, which was prevented by ET antagonist bosentan. To provide insight into the mechanism of glucose-induced and ET-mediated ED-B FN upregulation, we assayed endothelial cells (ECs). Inhibition of mitogen-activated protein kinase with pharmacological inhibitors and protein kinase B with dominant negative transfections prevented glucose- and ET-1-mediated FN and ED-B FN expression. Furthermore, treatment of cells exposed to high levels of glucose with ET antagonist prevented the activation of all signaling pathways studied and normalized glucose-induced ED-B FN expression. We then determined the functional significance of ED-B in ECs and show that ED-B FN is involved in vascular endothelial growth factor expression and cellular proliferation. These studies show that glucose-induced and ET-mediated FN and ED-B FN expressions involve complex interplays between signaling pathways and that ET may represent an ideal target for therapy in chronic diabetic complications.     

Formation of Umbilicaria decussata (Antarctic and Turkey) Extracts Based Nanoflowers with Their Peroxidase Mimic,Dye Degradation and Antimicrobial Properties

This work describes a unique and environmentally friendly approach for creating three-dimensional (3D) organic-inorganic flower shaped hybrid nanostructures called “nanoflower (NF)” by using Umbilicaria decussate (U. decussate) extract and copper ions (Cu²⁺). U. decussate species were collected from certain place in Antarctic and Turkey and extraction of each species were completed in methanol and water. The U. decussate extracts were used as organic components and Cu²⁺ acted as inorganic components for formation of U. decussate extracts based hybrid NFs. We rationally used these NFs as novel nanobiocatalyst and antimicrobial agents. These NFs exhibited peroxidase mimic, dye degradation and antimicrobial properties. The NFs were characterized with various techniques. For instance, the morphologies of the NFs were monitored by scanning electron microscope (SEM), presence of elements in the NFs were presented using Energy Dispersive X-Ray Analysis (EDX). Fourier-transform infrared spectroscopy (FT-IR) was used to elucidate corresponding bending and stretching of bonds in the NFs. The NFs acted as effective Fenton agents in the presence of hydrogen peroxide, and we demonstrated their peroxidase-like activity against guaiacol, dye degradation property towards malachite green and antimicrobial activity for Aeromonas hydrophila, Aeromonas sobria, Escherichia coli, Salmonella enterica and Staphylococcus aureus.     

Sinus Node Dysfunction as the First Manifestation of Left Ventricular Noncompaction with Multiple Cardiac Abnormalities

Left ventricular noncompaction (LVNC) is a genetically heterogenous form of cardiomyopathy which may remain undiagnosed till adulthood due to the late presentation of typical symptoms such as dyspnea, congestion, ventricular arrhythmias and thromboembolism. Symptomatic bradycardia secondary to persistent sinus node dysfunction is very rare. Coexistent cardiac defects are common in children however in adults the disease is usually in isolated form. Here, we present a case of twenty-three year-old female LVNC patient with patent ductus arteriosus, bicuspid aortic valve and persistent sinus node dysfunction who presented with dizziness as the first manifestation of the disease.     

Memantine,an Antagonist of the NMDA Glutamate Receptor,Affects Cell Proliferation,Differentiation and the Intracellular Cycle and Induces Apoptosis in Trypanosoma cruzi

Chagas'' disease is caused by the protozoan parasite Trypanosoma cruzi and affects approximately 10 million people in endemic areas of Mexico and Central and South America. Currently available chemotherapies are limited to two compounds: Nifurtimox and Benznidazole. Both drugs reduce the symptoms of the disease and mortality among infected individuals when used during the acute phase, but their efficacy during the chronic phase (during which the majority of cases are diagnosed) remains controversial. Moreover, these drugs have several side effects. The aim of this study was to evaluate the effect of Memantine, an antagonist of the glutamate receptor in the CNS of mammals, on the life cycle of T. cruzi. Memantine exhibited a trypanocidal effect, inhibiting the proliferation of epimastigotes (IC₅₀ 172.6 µM). Furthermore, this compound interfered with metacyclogenesis (approximately 30% reduction) and affected the energy metabolism of the parasite. In addition, Memantine triggered mechanisms that led to the apoptosis-like cell death of epimastigotes, with extracellular exposure of phosphatidylserine, increased production of reactive oxygen species, decreased ATP levels, increased intracellular Ca²⁺ and morphological changes. Moreover, Memantine interfered with the intracellular cycle of the parasite, specifically the amastigote stage (IC₅₀ 31 µM). Interestingly, the stages of the parasite life cycle that require more energy (epimastigote and amastigote) were more affected as were the processes of differentiation and cell invasion.     

Strategies of ROS regulation and antioxidant defense during transition from C3 to C4 photosynthesis in the genus Flaveria under PEG-induced osmotic stress

In the present study, we aimed to elucidate how strategies of reactive oxygen species (ROS) regulation and the antioxidant defense system changed during transition from C₃ to C₄ photosynthesis, by using the model genus Flaveria, which contains species belonging to different steps in C₄ evolution. For this reason, four Flaveria species that have different carboxylation mechanisms, Flaveria robusta (C₃), Flaveria anomala (C₃–C₄), Flaveria brownii (C₄-like) and Flaveria bidentis (C₄), were used. Physiological (growth, relative water content (RWC), osmotic potential), and photosynthetical parameters (stomatal conductance (g_s), assimilation rate (A), electron transport rate (ETR)), antioxidant defense enzymes (superoxide dismutase (SOD), catalase (CAT), peroxidase (POX), ascorbate peroxidase (APX), glutathione reductases(GR)) and their isoenzymes, non-enzymatic antioxidant contents (ascorbate, glutathione), NADPH oxidase (NOX) activity, hydrogen peroxide (H₂O₂) content and lipid peroxidation levels (TBARS) were measured comparatively under polyethylene glycol (PEG 6000) induced osmotic stress. Under non-stressed conditions, there was a correlation only between CAT (decreasing), APX and GR (both increasing) and the type of carboxylation pathways through C₃ to C₄ in Flaveria species. However, they responded differently to PEG-induced osmotic stress in regards to antioxidant defense. The greatest increase in H₂O₂ and TBARS content was observed in C₃F. robusta, while the least substantial increase was detected in C₄-like F. brownii and C₄F. bidentis, suggesting that oxidative stress is more effectively countered in C₄-like and C₄ species. This was achieved by a better induced enzymatic defense in F. bidentis (increased SOD, CAT, POX, and APX activity) and non-enzymatic antioxidants in F. brownii. As a response to PEG-induced oxidative stress, changes in activities of isoenzymes and also isoenzymatic patterns were observed in all Flaveria species, which might be related to ROS produced in different compartments of cells.     

Role of Aberrant Spontaneous Neurotransmission in SNAP25-Associated Encephalopathies

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