Atheroprotective role of vinpocetine: an old drug with new indication.

Endothelial dysfunction is considered one of the main causes of atherosclerosis and elevated blood pressure. Atherosclerosis (AS) formation is enhanced by different mechanisms including cytokine generation, vascular smooth muscle cell proliferation, and migration. One of the recent treatment toward endothelial dysfunction is vinpocetine (VPN). VPN is an ethyl apovincaminate used in the management of different cerebrovascular disorders and endothelial dysfunction through inhibition of atherosclerosis formation. VPN is a potent inhibitor of phosphodiesterase enzyme 1 (PDE1) as well it has anti-inflammatory and antioxidant effects through inhibition of the expression of nuclear factor kappa B (NF-κB). VPN has been shown to be effective against development and progression of AS. However, the underlying molecular mechanism was not fully clarified. Consequently, objective of the present narrative review was to clarify the mechanistic role of VPN in AS. Most of pro-inflammatory cytokines released from macrophages are inhibited by the action of VPN via NF-κB-dependent mechanism. VPN blocks monocyte adhesion and migration by inhibiting the expression of pro-inflammatory cytokines. As well, VPN is effective in reducing oxidative stress, a cornerstone in the pathogenesis of AS, through inhibition of NF-κB and PDE1. VPN promotes plaque stability and prevent erosion and rupture of atherosclerotic plaque. In conclusion, VPN through mitigation of inflammatory and oxidative stress with plaque stability effects could be effective agent in the management of endothelial dysfunction through inhibition of atherosclerosis mediators.

Is really endogenous ghrelin a hunger signal in chickens? Association of GHSR SNPs with increase appetite, growth traits, expression and serum level of GHRL, and GH.

Chicken growth hormone secretagogue receptor (GHSR) is a receptor for ghrelin (GHRL), a peptide hormone produced by chicken proventriculus, which stimulates growth hormone (GH) release and food intake. The purpose of this study was to search for single nucleotide polymorphisms (SNPs) in exon 2 of GHSR gene and to analyze their effect on the appetite, growth traits and expression levels of GHSR, GHRL, and GH genes as well as serum levels of GH and GHRL in Mandara chicken. Two adjacent SNPs, A239G and G244A, were detected in exon 2 of GHSR gene. G244A SNP was non-synonymous mutation and led to replacement of lysine amino acid (aa) by arginine aa, while A239G SNP was synonymous mutation. The combined genotypes of A239G and G244A SNPs produced three haplotypes; GG/GG, GG/AG, AG/AG, which associated significantly (P<0.05) with growth traits (body weight, average daily gain, shank length, keel length, chest circumference) at age from >4 to 16w. Chickens with the homozygous GG/GG haplotype showed higher growth performance than other chickens. The two SNPs were also correlated with mRNA levels of GHSR and GH (in pituitary gland), and GHRL (in proventriculus and hypothalamus) as well as with serum level of GH and GHRL. Also, chickens with GG/GG haplotype showed higher mRNA and serum levels. This is the first study to demonstrate that SNPs in GHSR can increase appetite, growth traits, expression and level of GHRL, suggesting a hunger signal role for endogenous GHRL.

Cellular fibronectin expression in chronic hepatitis C virus patients.

BACKGROUND: Hepatitis C virus (HCV) is associated with fibrosis, cirrhosis, hepatocellular carcinoma (HCC), and end-stage liver disease. In the normal liver, fibronectin plays crucial roles in various cellular functions, including cell adhesion, migration, proliferation, and differentiation. Increased expression of fibronectin is associated with areas of physiological or pathological tissue remodeling, including wound healing and tissue repair. The aim of the current study was to correlate the cellular fibronectin expression level in peripheral blood fibrocytes of chronic HCV patients with the severity of liver fibrosis as detected by liver biopsy. METHODS: The present study was conducted on 20 fibrotic liver cases with detectable HCV RNA, 10 HCV cirrhotic liver cases, and 10 control subjects of matched age and sex. Cellular fibronectin RNA was detected by PCR. RESULTS: The mean level of cellular fibronectin expression in cases with liver fibrosis was significantly higher than the corresponding level in cases with liver cirrhosis (p = 0.019). Control individuals did not express cellular fibronectin. There was also a significant correlation between the Metavir score and cellular fibronectin RNA, APRI, and FIB-4 scores. However, based on the area under the curve (AUC) values, cellular fibronectin showed a lower diagnostic performance than APRI and FIB-4 scores. CONCLUSIONS: Cellular fibronectin RNA showed satisfactory reproducibility and could be used to differentiate HCV fibrotic liver (F1-F3) and HCV cirrhotic liver (F4) from normal liver (F0).

The Parasites Caught In-Action: Imaging at the Host-Parasite Interface.

For many decades, scientists were unable to expose the invisible existence of the parasites in their living hosts, except by scarification and then dissection of the animal model. This process just demonstrates a dead parasite in a dead host. Using this approach, very limited information can be obtained concerning the dynamics of infection and the pathways utilized by the parasite to survive within a hostile host's environment. Introduction of ultra-high-speed imaging techniques, with a time domain of barely few microseconds or even less, has revolutionized the "in vivo dissection" of the parasites. Such methods provide platforms for imaging host-parasite interactions at diverse scales, down to the molecular level. These have complementary advantages and relative assets in investigating host-parasite interactions. Therefore, better elucidation of such interaction may require the usage of more than one approach. Precise in vivo quantification, of the parasite load within the host, and better insight into the kinetics of infection are the two main advantages of the novel imaging procedures. However, imaging parasite-host interplay is still a challenging approach due to many constraints related to the parasite biology, the tissue environment within which the parasites exist, and the logistic technical limitations. This review was planned to assist better understanding of how much the new imaging techniques impacted the recent advances in parasite biology, especially the immunobiology of protozoan parasites.

The impact of omeprazole on mycophenolate pharmacokinetics in kidney transplant recipients.

BACKGROUND: The absorption rates of mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS) may be influenced by the concomitant use of omeprazole. METHODS: One hundred kidney transplant patients were recruited during their outpatient visits, including 50 on MMF and 50 on EC-MPS. At the clinic, a predose mycophenolic acid (MPA) sample (C0) was collected; subsequently, the participants received the proton-pump inhibitor omeprazole along with either MMF or EC-MPS. Two more blood samples were collected at 1.5 and 3.5 hours and used to estimate an area under the curve (AUC) from zero to 12 hours [AUC (0-12)]. RESULTS: The mean number of months after transplant was 92 months. The median AUC (0-12) and C0 results were 62.2 mg·h/L and 2.0 mg/L for the MMF group and 71.9 mg·h/L and 1.8 mg/L for the EC-MPS group (P = 0.160 and 0.225, respectively). Interestingly, 54% of the MMF group and 62% of the EC-MPS group showed AUCs above the target values. The correlation between MPA C0 and the predicted AUC was poor in both groups. CONCLUSION: Omeprazole can be safely co-administered with either MMF or EC-MPS, as it did not compromise the MPA exposure. Unexpectedly, however, a high percentage of patients presented MPA AUCs exceeding the target value, highlighting the importance of periodically assessing MPA level.

Investigation of Biochemical Alterations in Ischemic Stroke Using Fourier Transform Infrared Imaging Spectroscopy-A Preliminary Study.

OBJECTIVE: Brain damage, long-term disability and death are the dreadful consequences of ischemic stroke. It causes imbalance in the biochemical constituents that distorts the brain dynamics. Understanding the sub-cellular alterations associated with the stroke will contribute to deeper molecular understanding of brain plasticity and recovery. Current routine approaches examining lipid and protein biochemical changes post stoke can be difficult. Fourier Transform Infrared (FTIR) imaging spectroscopy can play a vital role in detecting these molecular alterations on a sub-cellular level due to its high spatial resolution, accuracy and sensitivity. This study investigates the biochemical and molecular changes in peri-infract zone (PIZ) (contiguous area not completely damaged by stroke) and ipsi-lesional white matter (WM) (right below the stroke and PIZ regions) nine weeks post photothrombotic ischemic stroke in rats. MATERIALS AND METHODS: FTIR imaging spectroscopy and transmission electron microscopy (TEM) techniques were applied to investigate brain tissue samples while hematoxylin and eosin (H&E) stained images of adjacent sections were prepared for comparison and examination the morphological changes post stroke. RESULTS: TEM results revealed shearing of myelin sheaths and loss of cell membrane, structure and integrity after ischemic stroke. FTIR results showed that ipsi-lesional PIZ and WM experienced reduction in total protein and total lipid content compared to contra-lesional hemisphere. The lipid/protein ratio reduced in PIZ and adjacent WM indicated lipid peroxidation, which results in lipid chain fragmentation and an increase in olefinic content. Protein structural change is observed in PIZ due to the shift from random coli and α-helical structures to ß-sheet conformation. CONCLUSION: FTIR imaging bio-spectroscopy provide novel biochemical information at sub-cellular levels that be difficult to be obtained by routine approaches. The results suggest that successful therapeutic strategy that is based on administration of anti-oxidant therapy, which could reduce and prevent neurotoxicity by scavenging the lipid peroxidation products. This approach will mitigate tissue damage in chronic ischemic period. FTIR imaging bio-spectroscopy can be used as a powerful tool and offer new approach in stroke and neurodegenerative diseases research.

AEO7 Surfactant as an Eco-Friendly Corrosion Inhibitor for Carbon Steel in HCl solution.

The impact of AEO7 surfactant on the corrosion inhibition of carbon steel (C-steel) in 0.5 M HCl solution at temperatures between 20 °C and 50 °C was elucidated using weight loss and different electrochemical techniques. The kinetics and thermodynamic parameters of the corrosion and inhibition processes were reported. The corrosion inhibition efficiency (IE%) improved as the concentration of AEO7 increased. In addition, a synergistic effect was observed when a concentration of 1 × 10-3 mol L-1 or higher of potassium iodide (KI) was added to 40 µmol L-1 of the AEO7 inhibitor where the corrosion IE% increased from 87.4% to 99.2%. Also, it was found that the adsorption of AEO7 surfactant on C-steel surface followed the Freundlich isotherm. Furthermore, electrochemical impedance spectroscopy (EIS) and potentiodynamic polarization measurements indicated that AEO7 was physically adsorbed on the steel surface. The surface topography was examined using an optical profilometer, an atomic force microscope (AFM), and a scanning electron-microscope (SEM) coupled with an energy dispersion X-ray (EDX) unit. Quantum chemical calculations based on the density functional theory were performed to understand the relationship between the corrosion IE% and the molecular structure of the AEO7 molecule.

More Than an Association: Latent Toxoplasmosis Might Provoke a Local Oxidative Stress That Triggers the Development of Bipolar Disorder.

INTRODUCTION: Toxoplasma gondii, a common parasitic infection, has a special affinity to the brain. It has a lifelong existence without an apparent clinical disease. While the etiology of bipolar disorder (BD) remains unclear, epidemiological studies suggest a role for infections. Central nervous system is particularly susceptible to oxidative stress (OS) because of its high metabolic rate and its low levels of antioxidant defenses. OS is a contributor to the initiation and progression of many neurological illnesses. OS injury is a constantly and compelling finding associated with BD and toxoplasmosis. AIM: This cross-sectional study has investigated a possible role of toxoplasma-induced OS in the development of BD. METHODS: Healthy controls and BD patients were examined for anti-Toxoplasma immunoglobulin-G (IgG) and two protein (3-nitrotyrosine) and DNA (8-hydroxy-2' deoxyguanosine [8-OHdG]) OS markers. RESULTS: Toxoplasma positivity was higher (40%) among BD patients compared to controls (12%). Significantly higher levels of anti-Toxoplasma IgG were detected in BD patients compared to controls. Nitrotyrosine (796.7 ± 106.28) and especially 8-OHdG (20.31 ± 8.38) were significantly higher among toxo-positive BD compared to toxo-negative BD (675.97 ± 144.19 and 7.44 ± 2.86) and healthy controls (464.02 ± 134.6 and 4.17 ± 1.43). CONCLUSION: These findings might indicate a role for Toxoplasma infection in the development of BD, possibly through creating a highly oxidative brain environment.

Genetic diversity among natural populations of Schistosoma haematobium might contribute to inconsistent virulence and diverse clinical outcomes.

There is an evident difference in the intensity of morbidity caused by Schistosoma haematobium in North-African zones compared to Sub-Saharan ones. Clinical outcome dichotomy corresponds to two geographically distinct intermediate host snail species that are only infected by the related strain of the parasite. In concert, there is a manifest hybridization of the parasite with other Schistosoma species confined to certain regions of Africa. This raises a reasonable suggestion that S. haematobium has no less than two phylogenetic clusters that have different virulence. The aim of the study was to examine the possible diversity among S. haematobium using simultaneous amplification of genomic DNA of selected isolates. Random amplified polymorphic DNA-polymerase chain reaction markers were used to study the genetic diversity among S. haematobium natural isolates from selected regions of Africa (Egypt, Zimbabwe, and South Africa) that represent different ecological conditions, different species of intermediate host, and different possibilities of field hybridization with other schistosomes. A moderate to high level of genetic diversity was evident among the three isolates. More bands were shared by the isolates from Zimbabwe and South Africa (similarity index = 0.721) than those shared by each with the Egyptian isolate (similarity index = 0.551 and 0.566, respectively), suggesting that at least two phylogenetic groups of S. haematobium do exist in distinct geographic regions of Africa. The elucidation of the possible genetic diversity among S. haematobium parasites may explain many ambiguous aspects of the biology of the parasite-like virulence, immune evasion and drug resistance.

The immunomodulatory effects of rolipram abolish drug-resistant latent phase of Toxoplasma gondii infection in a murine model.

BACKGROUND: Latent toxoplasmosis always has the risk of reactivation leading to significant sequelae. The available medications, for chronic toxoplasmosis, are awfully limited by resistance of Toxoplasma cysts. Therefore, there is a growing necessity for novel therapeutic approaches. Agents increasing cAMP levels and downregulating proinflammatory cytokine could inhibit Toxoplasma conversion to the bradyzoite stage. This study explores a potential immunomodulatory effect of rolipram, a PDE4 inhibitor, on the course of experimental toxoplasmosis and links this role to deterrence of the resistant chronic phase of the disease. MATERIALS AND METHODS: Mice infected with low pathogenic strain of Toxoplasma gondii were treated with rolipram for three weeks. The effect of rolipram was evaluated through tissue injury scoring, brain cyst count, specific IgG titers as well as TNF-α, IFN-γ and IL-12 assays. RESULTS: Rolipram was partially able to prevent the progression to chronic toxoplasmosis. Toxoplasma brain cyst burden showed a 74% reduction while Toxoplasma-induced inflammatory foci per liver area and nucleated cells per inflammatory focus were significantly reduced: 57.14% and 61.3% respectively. Significant reduction of TNF-α (84.6%), IFN-γ (76.7%) and IL-12 (71%) levels was demonstrated along with significant inhibition of anti-Toxoplasma antibody response. CONCLUSION: Rolipram efficiently modulated the Toxoplasma-induced immunological changes with a consequent remission of chronic toxoplasmosis. This study is the first to report the utilization of PDE4 inhibitors as possible immune modulators of chronic phase of Toxoplasma infection.

Parasites-allergy paradox: Disease mediators or therapeutic modulators.

The noticeable phenomenon of an increased frequency of immune-inflammatory disorders, in the industrialized world, has led to the implication of parasitic infections in the pathophysiology of these diseases. Most of the studies investigated the infection connection to allergy have centered on helminthes. Parasitic helminthes are a group of metazoans that are evolutionary diverse, yet converge to evolve common modes of immunomodulation. Helminth immunoregulation is mainly mediated by a regulatory response including Treg and Breg cells with alternatively-activated macrophages. There is increasing evidence for a causal relationship between helminth infection and allergic hyporesponsiveness, however, conflicting data are still generating. The helminth immunoregulation seems to be species-specific and phase-specific. It depends on the stage of the clinical disease which correlates with a corresponding parasitic stage (egg, larva or mature adult). Here, we review the cellular and molecular mechanisms utilized by helminthes to manipulate the immune system and the consequent bystander immunomodulatory responses toward environmental allergens. We especially focus on parasitic species and molecules involved in the modulation of allergic disorders and summarize the experimental and clinical trials using them as therapeutic agents. We also discuss the potentials and obstacles, for helminthes and/or their derived molecules, to emerge as novel therapeutic modalities.

A new focus of autochthonous transmission of Cordylobia anthropophaga in Saudi Arabia.

BACKGROUND: Cordylobia anthropophaga, is responsible for nodular cutaneous myiasis in sub-Saharan Africa. The fly has long been limited to tropical Africa except for Asir Province, Saudi Arabia. Al Baha Province; north of Asir has an ecological pattern close to that dominant in subtropical Africa. The Southern parts of Saudi Arabia, including Al Baha, are considered part of the Afro-tropical zoogeographical belt where C. anthropophaga is dominant. A case, with cutaneous nodular lesions, was presented to us, where comprehensive investigations were done to establish the diagnosis and to relate it to the known epidemiological background. MATERIALS AND METHODS: A thorough history taking, comprehensive clinical examination and an intensive parasitological examination on a viable larva recovered from the cutaneous lesions, were performed. Taxonomic identification of the larva was done based on various criteria including shape, size, cuticle spine pattern and the posterior spiracles of the recovered larva. RESULTS: We report a case of cutaneous myiasis, caused by Cordylobia anthropophaga, indigenously acquired in Al-Baha. The recovered larva was identified as the third instar of C. anthropophaga. With no history of travel to Africa or to Asir, along with a comprehensive epidemiological assessment, an autochthonous pattern of transmission was confirmed. CONCLUSION: We present a new focus of autochthonous transmission of C. anthropophaga in Saudi Arabia suggesting a need for an epidemiological reassessment. We also propose considering Cordylobia myiasis as a differential diagnosis in furuncular skin lesions, even in individuals with no history of traveling to Africa.

Serological evidences link toxoplasmosis with schizophrenia and major depression disorder.

The etiology of psychiatric disorders is largely unknown. A role of environmental insults during early neurodevelopment have been suggested. Infections are possible risk factors for psychiatric disorders especially Toxoplasma gondii, a neurotropic parasite with a lifelong residence in brain. This study has investigated a possible role of toxoplasmosis in the development of schizophrenia and major depression disorder (MDD). The influence of other covariates; age, gender and family history was also studied. A cross-sectional study on a total of 177 individuals, where anti-Toxoplasma IgG and IgM in sera of schizophrenia (n = 63) and MDD (n = 39) patients, all fulfilling DSM-5 diagnostic criteria, were compared to healthy volunteers (n = 55). Toxoplasma positivity was highest (31.75%) among schizophrenics followed by MDD (25.64%) and controls (14.55%). IgG levels were significantly higher in toxo-positive schizophrenics (230.1 ± 22.9) and MDD (220.56 ± 24.8) compared to controls (9.98 ±1.78). Three patients only, all schizophrenic, have positive IgM antibodies. Age and male gender appear to have positive associations to toxoplasmosis and psychiatric disorders while family history has no obvious additive role. This report is one of few linking Toxoplasma infection to MDD and adds to many suggesting a link between latent toxoplasmosis and schizophrenia.

Application of adult worm and lung-stage antigens to immunize against Schistosoma mansoni using cytokines as adjuvants.

Different Schistosoma mansoni antigens; adult worm antigen (SWAP) and lung-stage antigen (SLAP) together with different cytokine adjuvants (Interferon-gamma and Interleukin-4) were used to immunize mice against. S. mansoni. Immunization program was directed towards the production of an intense immune response together with balanced T-helper1 and T-helper2 immune responses. The goal of immunization was not only to protect from infection but also to modulate the pathology inflicted by the parasite. Parameters like adult load, egg counts, anti-Schistosoma antibody titers and liver pathology were used to evaluate the different immunization scheme. SLAP antigen has proven to be a better antigen not only in protection but also in pathology modulation. SLAP plus IFN-gamma as an adjuvant was the best immunization regimen with almost 50% protection and a remarkable resolving of parasite pathology. Unexpectedly, IL-4 had a weak but observed adjuvant protective effect. The results is a step in the path for a Schistosoma vaccine that guides the immune system towards a balanced response targeting the pathology induced by the parasite rather than the parasite itself.