The hepatoprotective effects of Hypericum perforatum L. on hepatic ischemia/reperfusion injury in rats

Little is known about the effective role of Hypericum perforatum on hepatic ischemia–reperfusion (I/R) injury in rats. Hence, albino rats were subjected to 45 min of hepatic ischemia followed by 60 min of reperfusion period. Hypericum perforatum extract (HPE) at the dose of 50 mg/kg body weight (HPE₅₀) was intraperitonally injected as a single dose, 15 min prior to ischemia. Rats were sacrificed at the end of reperfusion period and then, biochemical investigations were made in serum and liver tissue. Liver tissue homogenates were used for the measurement of malondialdehyde (MDA), catalase (CAT) and glutathione peroxidase (GPx) levels. At the same time alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) were assayed in serum samples and compared statistically. While the ALT, AST, LDH activities and MDA levels were significantly increased, CAT and GPx activities significantly decreased in only I/R-induced control rats compared to normal control rats (p < 0.05). Treatment with HPE₅₀ significantly decreased the ALT, AST, LDH activities and MDA levels, and markedly increased activities of CAT and GPx in tissue homogenates compared to I/R-induced rats without treatment–control group (p < 0.05). In oxidative stress generated by hepatic ischemia–reperfusion, H. perforatum L. as an antioxidant agent contributes an alteration in the delicate balance between the scavenging capacity of antioxidant defence systems and free radicals in favour of the antioxidant defence systems in the body.     

Carvacrol partially reverses symptoms of diabetes in STZ-induced diabetic rats

Little is known about the protective effects of carvacrol on the symptoms of streptozotocin induced diabetes in rats. Hence, this present study was designed to evaluate the protective effect of the strong antioxidant, carvacrol, on the symptoms of streptozotocin induced diabetes in rats. Carvacrol at the doses of 25 and 50 mg/kg body weight were orally administered to diabetic rats for a period of 7 days after the onset of diabetes. Food-water intake and body weight changes were daily recorded. Biochemical parameters such as serum glucose, insulin, total cholesterol, alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase were measured. Although treatment of diabetic rats with oral administration of carvacrol resulted in a slight reduction in serum glucose level and significant reduction in serum total cholesterol, alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase in comparison with diabetic control rats, there were no significant differences in serum insulin levels, food-water intake values and body weight changes. Despite the inadequacy of carvacrol on diabetes treatments, it was determined to have at least a partially protective role on liver enzymes.     

Aneurysm and Helicobacter pylori relationship: the seropositivity of CagA, VacA and other antigens of Helicobacter pylori in abdominal and ascending aortic aneurysms

Helicobacter pylori is thought to be related to atherosclerosis and aneurysm development. We aimed to detect virulance factors of H. pylori and examine the potential etiopathogenetic relationship between aortic aneurysm and H. pylori, 58 abdominal aortic aneurysm (AAA) and 38 ascending aortic aneurysm (AsAA) cases and 57 Healty control group (HCG) were included. We investigated H. pylori IgG by ELISA and virulance factors by Western-Blot (WB) method. No difference was found between AAA (67.24%), AsAA (73.68%) and HCG (57.89%) for H. pylori IgG (p > 0.05). A significant difference was found between AsAA (78.95%) and HCG (57.89%) for H.pylori IgG (p < 0.05) by ELISA and a significant difference was found only between AsAA (100%) and HCG (37.5%) for H. pylori IgG in the 45-55 age group by WB. A statistically significant difference was found between AAA and AsAA for VacA and CagA + VacA and CagA + VacA + UreA antigens and also a significant difference was found between AsAA and HCG for CagA + UreA antigens (p < 0.05). Finally, we suggest that H. pylori VacA has a more important role than CagA in the development of two aneurysms especially in ruptured AAA. New extended studies detecting H. pylori DNA are needed to detect the aetiopathogenesis between aneurysm types and H. pylori.     

Selected trace elements and esterase activity of carbonic anhydrase levels in lambs with pneumonia

The levels of, zinc, copper, Fe, Zn, Cu, Mn, Mg, K, Na, and Cl and the activity of carbonic anhydrase were determined in lambs with pneumonia. A significant decrease of p<0.01 level in Zn concentration, in Cu level (p<0.001) and significant increases in K and Na levels (p<0.05) and of the Cu/Zn ratio (p<0.001) were observed in the study group. The carbonic anhydrase activity was decreased in the study group, but the decrease was not statistically significant (p>0.05). Also, nonsignificant decreases of Fe, Mg, and Cl and increase of the Mn concentration were also observed in the lambs with pneumonia (p>0.05). Our results suggest that the significant element changes reported here and the Cu/Zn ratio, but not the activity of carbonic anhydrase, can be used as indicators of pneumococcal infection.     

Proteome of Hydra nematocyst

Stinging cells or nematocytes of jellyfish and other cnidarians represent one of the most poisonous and sophisticated cellular inventions in animal evolution. This ancient cell type is unique in containing a giant secretory vesicle derived from the Golgi apparatus. The organelle structure within the vesicle comprises an elastically stretched capsule (nematocyst) to which a long tubule is attached. During exocytosis, the barbed part of the tubule is accelerated with >5 million g in <700 ns, enabling a harpoon-like discharge (Nüchter, T., Benoit, M., Engel, U., Ozbek, S., and Holstein, T. W. (2006) Curr. Biol. 16, R316-R318). Hitherto, the molecular components responsible for the organelle's biomechanical properties were largely unknown. Here, we describe the proteome of nematocysts from the freshwater polyp Hydra magnipapillata. Our analysis revealed an unexpectedly complex secretome of 410 proteins with venomous and lytic but also adhesive or fibrous properties. In particular, the insoluble fraction of the nematocyst represents a functional extracellular matrix structure of collagenous and elastic nature. This finding suggests an evolutionary scenario in which exocytic vesicles harboring a venomous secretome assembled a sophisticated predatory structure from extracellular matrix motif proteins.     

Structure-activity analysis of the dermcidin-derived peptide DCD-1L, an anionic antimicrobial peptide present in human sweat

Dermcidin encodes the anionic amphiphilic peptide DCD-1L, which displays a broad spectrum of antimicrobial activity under conditions resembling those in human sweat. Here, we have investigated its mode of antimicrobial activity. We found that DCD-1L interacts preferentially with negatively charged bacterial phospholipids with a helix axis that is aligned flat on a lipid bilayer surface. Upon interaction with lipid bilayers DCD-1L forms oligomeric complexes that are stabilized by Zn(2+). DCD-1L is able to form ion channels in the bacterial membrane, and we propose that Zn(2+)-induced self-assembly of DCD-1L upon interaction with bacterial lipid bilayers is a prerequisite for ion channel formation. These data allow us for the first time to propose a molecular model for the antimicrobial mechanism of a naturally processed human anionic peptide that is active under the harsh conditions present in human sweat.     

A Non-sulfated Chondroitin Stabilizes Membrane Tubulation in Cnidarian Organelles

Membrane tubulation is generally associated with rearrangements of the cytoskeleton and other cytoplasmic factors. Little is known about the contribution of extracellular matrix components to this process. Here, we demonstrate an essential role of proteoglycans in the tubulation of the cnidarian nematocyst vesicle. The morphogenesis of this extrusive organelle takes place inside a giant post-Golgi vesicle, which topologically represents extracellular space. This process includes the formation of a complex collagenous capsule structure that elongates into a long tubule, which invaginates after its completion. We show that a non-sulfated chondroitin appears as a scaffold in early morphogenesis of all nematocyst types in Hydra and Nematostella. It accompanies the tubulation of the vesicle membrane forming a provisional tubule structure, which after invagination matures by collagen incorporation. Inhibition of chondroitin synthesis by β-xylosides arrests nematocyst morphogenesis at different stages of tubule outgrowth resulting in retention of tubule material and a depletion of mature capsules in the tentacles of hydra. Our data suggest a conserved role of proteoglycans in the stabilization of a membrane protrusion as an essential step in organelle morphogenesis.     

Colchicine Modulates Oxidative Stress in Serum and Neutrophil of Patients with Behçet Disease Through Regulation of Ca<Superscript>2+</Superscript> Release and Antioxidant System

Behçet disease (BD) is a chronic, inflammatory, and multisystemic condition with an uncertain pathogenesis. One of the major immunologic findings in BD pathogenesis is increase in activity of neutrophil. An increase in the cytosolic free Ca²⁺ [Ca²⁺]_i concentration that induces Ca²⁺ signaling is an important step that participates in the neutrophil activation and reactive oxygen species production that leads to tissue damage in body cells. We aimed to investigate the effects of colchicine on oxidative stress and Ca²⁺ release in serum and neutrophil of BD patients with active and inactive periods. Twelve Behçet patients (6 active and 6 inactive) and 6 control subject were included in the study. Disease activity was considered by clinical findings. Serum and neutrophil samples were obtained from the patients and control subjects. Neutrophils from patients with active BD were divided into three subgroups and were incubated with colchicine, verapamil + diltiazem, and colchicine + verapamil + diltiazem, respectively. Erythrocyte sedimentation rate, leucocytes counts, serum C-reactive protein, neutrophil, and serum lipid peroxidation and intracellular Ca²⁺ release levels were higher in active and inactive groups than in the control group, although their levels were lower in active group than in inactive group. However, neutrophil Ca²⁺ release levels were decreased in colchicine, verapamil + diltiazem, and colchicine + verapamil + diltiazem groups group compared to active group. Serum glutathione, vitamin A, vitamin E, and β-carotene concentrations were lower in active and inactive groups than in the control group, although serum vitamin E and β-carotene concentrations were higher in the inactive group than in the active group. Neutrophil and serum glutathione peroxidase activity within the three groups did not change. In conclusion, we observed the importance of Ca²⁺ influx into the neutrophils and oxidative stress in the pathogenesis and activation of the patients with BD. Colchicine induced protective effects on oxidative stress by modulating Ca²⁺ influx in BD patients.     

A Mycobacterium marinum TesA mutant defective for major cell wall-associated lipids is highly attenuated in Dictyostelium discoideum and zebrafish embryos

Infection of the zebrafish with Mycobacterium marinum is regarded as a well-established experimental model to study the pathogenicity of Mycobacterium tuberculosis. Herein, a M. marinum transposon mutant library was screened for attenuated M. marinum phenotypes using a Dictyostelium discoideum assay. In one attenuated mutant, the transposon was located within tesA, encoding a putative type II thioesterase. Thin-layer chromatography analyses indicated that the tesA::Tn mutant failed to produce two major cell wall-associated lipids. Mass spectrometry and nuclear magnetic resonance clearly established the nature of missing lipids as phthioglycol diphthioceranates and phenolic glycolipids, respectively, indicating that TesA is required for the synthesis of both lipids. When injected into the zebrafish embryo bloodstream, the mutant was found to be highly attenuated, thus validating the performance and relevance of the Dictyostelium screen. Consistent with these in vivo findings, tesA::Tn exhibited increased permeability defects in vitro, which may explain its failure to survive in host macrophages. Unexpectedly, virulence was retained when bacteria were injected into the notochord. Histological and ultrastructural studies of the infected notochord revealed the presence of actively proliferating mycobacteria, leading to larval death. This work presents for the first time the notochord as a compartment highly susceptible to mycobacterial infection.