Oxidative stress may be a contributing factor in fibromyalgia patients' pain mechanisms.

OBJECTIVE: The pathophysiology of fibromyalgia (FM), a continuously painful syndrome with no known origin, has been related to mitochondrial dysfunction, oxidative stress, and inflammation. Recent studies have shown that FM may be associated with an oxidative balance disorder. The objective of this study was to measure the levels of oxidative stress in FM patients and try to understand the association between FM and free radicals. METHODS: This study was performed on 100 volunteers admitted to the University of Health Sciences, Sultan 2, Abdulhamid Han Health Application and Research Center Physical Therapy and Rehabilitation Clinic, including 50 healthy controls and 50 patients with FM. To analyze oxidative stress biomarkers, total oxidant status (TOS) and total antioxidant status (TAS) levels were measured. Total thiol (TT) and native thiol (NT) concentrations were measured to determine the relationship between thiol groups. Disulfide (DIS) and oxidative stress index (OSI) were calculated with mathematical formulas. RESULTS: While TOS and OSI levels were statistically higher in FM patients, TAS levels were significantly lower compared to the healthy control group (p<0.001). In comparison to the healthy control group, FM patients had considerably decreased TT and NT levels. DIS levels were significantly higher in FM patients than in controls (p<0.001). CONCLUSIONS: Reactive oxygen species have several negative impacts on the human body. As a result of the measurements we analyzed, the relationship between FM and oxidative stress should be studied in terms of disease progression and may help improve the treatment process.

SCREENING OF PROP-1, LHX2 AND POU1F1 MUTATIONS IN PATIENTS WITH ECTOPIC POSTERIOR PITUITARY GLAND.

OBJECTIVE: Ectopic posterior pituitary gland (EPP) is usually characterized by an abnormal pituitary stalk and hypoplasia of the anterior hypophysis. The genetic mechanisms involved in the development of EPP remain uncertain. The aim of this study is to determine whether mutations in the three genes, PROP-1, LHX2, and POU1F1, are associated with the risk for and the characteristics of EPP. METHODS: In the Endocrinology Outpatient Clinic of "Dr. Behcet Uz" Children's Hospital, 27 patients with EPP were submitted to sequencing analyses of the PROP-1, LHX2, and POU1F1 genes. RESULTS: Growth hormone, thyrotropin, corticotropin, gonadotropin, and vasopressin deficiency were observed in 22 (81.5%), 23 (85.2%), 17 (63%), 14 (51.9%), and two (7.4%) patients. Thirteen patients (48.1%) presented with hyperprolactinemia. Fourteen patients (51%) had a history of birth dystocia, and 12 cases (42.1%) had a history of breech presentation. Central nervous system abnormalities included five cases with corpus callosum agenesis, one case with schizencephaly, and one case with Chiari type 1 malformation. We identified a homozygous p.S109* mutation in exon 2 in one male patient with EPP and two different PROP1 gene polymorphisms (A142T or c.109+3 G>A polymorphism) in thirteen patients. CONCLUSIONS: Our results suggest that PROP1 gene abnormalities might explain the genetic mechanisms involved in the development of EPP.

Frequent migration of introduced cucurbit-infecting begomoviruses among Middle Eastern countries.

BACKGROUND: In the early 2000s, two cucurbit-infecting begomoviruses were introduced into the eastern Mediterranean basin: the Old World Squash leaf curl virus (SLCV) and the New World Watermelon chlorotic stunt virus (WmCSV). These viruses have been emerging in parallel over the last decade in Egypt, Israel, Jordan, Lebanon and Palestine. METHODS: We explored this unique situation by assessing the diversity and biogeography of the DNA-A component of SLCV and WmCSV in these five countries. RESULTS: There was fairly low sequence variation in both begomovirus species (SLCV π = 0.0077; WmCSV π = 0.0066). Both viruses may have been introduced only once into the eastern Mediterranean basin, but once established, these viruses readily moved across country boundaries. SLCV has been introduced at least twice into each of all five countries based on the absence of monophyletic clades. Similarly, WmCSV has been introduced multiple times into Jordan, Israel and Palestine. CONCLUSIONS: We predict that uncontrolled movement of whiteflies among countries in this region will continue to cause SLCV and WmCSV migration, preventing strong genetic differentiation of these viruses among these countries.

Plant-based vaccines: novel and low-cost possible route for Mediterranean innovative vaccination strategies.

A plant bioreactor has enormous capability as a system that supports many biological activities, that is, production of plant bodies, virus-like particles (VLPs), and vaccines. Foreign gene expression is an efficient mechanism for getting protein vaccines against different human viral and nonviral diseases. Plants make it easy to deal with safe, inexpensive, and provide trouble-free storage. The broad spectrum of safe gene promoters is being used to avoid risk assessments. Engineered virus-based vectors have no side effect. The process can be manipulated as follows: (a) retrieve and select gene encoding, use an antigenic protein from GenBank and/or from a viral-genome sequence, (b) design and construct hybrid-virus vectors (viral vector with a gene of interest) eventually flanked by plant-specific genetic regulatory elements for constitutive expression for obtaining chimeric virus, (c) gene transformation and/or transfection, for transient expression, into a plant-host model, that is, tobacco, to get protocols processed positively, and then moving into edible host plants, (d) confirmation of protein expression by bioassay, PCR-associated tests (RT-PCR), Northern and Western blotting analysis, and serological assay (ELISA), (e) expression for adjuvant recombinant protein seeking better antigenicity, (f) extraction and purification of expressed protein for identification and dosing, (g) antigenicity capability evaluated using parental or oral delivery in animal models (mice and/or rabbit immunization), and (h) growing of construct-treated edible crops in protective green houses. Some successful cases of heterologous gene-expressed protein, as edible vaccine, are being discussed, that is, hepatitis C virus (HCV). R9 mimotope, also named hypervariable region 1 (HVR1), was derived from the HVR1 of HCV. It was used as a potential neutralizing epitope of HCV. The mimotope was expressed using cucumber mosaic virus coat protein (CP), alfalfa mosaic virus CP P3/RNA3, and tobacco mosaic virus (TMV) CP-tobacco mild green mosaic virus (TMGMV) CP as expression vectors into tobacco plants. Expressed recombinant protein has not only been confirmed as a therapeutic but also as a diagnostic tool. Herpes simplex virus 2 (HSV-2), HSV-2 gD, and HSV-2 VP16 subunits were transfected into tobacco plants, using TMV CP-TMGMV CP expression vectors.

Association of serum paraoxonase activity and coronary artery calcification.

AIM: It has been known that there was a relation between the activities of serum paraoxonase (PON) and the severity of the coronary artery disease. However, little is known about association of coronary artery calcification (CAC) and serum PON activities. The aim of this study is to evaluate the relationship between CAC and serum PON activities. PATIENTS AND METHODS: We measure serum PON activities from 122 patients (42 female, mean age = 62±10 years) with angiographically documented CAC (Group I), and 138 patients (54 female, mean age = 60±10 years) without CAC (Group II). Coronary calcification was detected with fluoroscopy before coronary angiography. Serum PON activities were measured by spectrophotometrically method. Patient characteristics and baseline data were recorded from patient's files. RESULTS: The triglyceride levels is lower in group I than group II (p = 0.040). Diastolic blood pressure and frequency of diabetes mellitus was higher in the group I than group II (respectively p = 0.012 and p = 0.022). The other clinic and laboratory parameters were similar in two groups (all p > 0.05). The only statistically significant differences between with CAC and without CAC groups in respect to serum PON activities were present (170.6 ± 59.6 vs. 209.6 ± 69.8 U/ml; respectively, p < 0.001). There was a negative correlation between serum PON activities and presence of CAC (p < 0.001). CONCLUSIONS: These data indicate that the serum PON activities are decreased in patients with CAC. The serum PON activities may play a role in development of the CAC and reduced serum PON activity might represent a biochemical marker of CAC.

Identification of neurons specifically activated after recall of context fear conditioning.

The learning of new information and recall of that information presumably involves modification of and access to shared circuitry in the brain. However, learning and recall may involve the activation of distinct parts of that circuitry, according to the quite distinct functional differences between these two processes. Previously we examined neuronal activation following learning of context fear conditioning. Using the Fos-Tau-LacZ (FTL) transgenic mouse to label activated neurons, we identified a number of distinct populations of neurons in amygdala and hypothalamus which showed learning specific activation. These populations of neurons showed much less activation following recall. Here we ask what populations of neurons might be specifically activated following recall. We trained mice in context fear conditioning, and then looked at FTL activation following recall of context fear. We identified a number of populations of neurons which showed recall specific activation in nucleus accumbens shell, the anterio-medial bed nucleus of stria terminalis, the anterior commissural nucleus and the periventricular hypothalamic nucleus. These were all different populations of neurons compared with those activated following context fear learning. These different functional activation patterns occurring between learning and recall may reflect the different brain functions occurring between these two memory related processes.

Diagnosis and control of cereal viruses in the Middle East.

Middle Eastern countries are major consumers of small grain cereals. Egypt is the biggest bread wheat producer with 7.4 million tons (MT) in 2007, but at the same time, it had to import 5.9 MT. Jordan and Israel import almost all the grains they consume. Viruses are the major pathogens that impair grain production in the Middle East, infecting in some years more than 80% of the crop. They are transmitted in nonpersistent, semipersistent, and persistent manners by insects (aphids, leafhoppers, and mites), and through soil and seeds. Hence, cereal viruses have to be controlled, not only in the field but also through the collaborative efforts of the plant quarantine services inland and at the borders, involving all the Middle Eastern countries. Diagnosis of cereal viruses may include symptom observation, immunological technologies such as ELISA using polyclonal and monoclonal antibodies raised against virus coat protein expressed in bacteria, and molecular techniques such as PCR, microarrays, and deep sequencing. In this chapter, we explore the different diagnoses, typing, and detection techniques of cereal viruses available to the Middle Eastern countries. We highlight the plant quarantine service and the prevention methods. Finally, we review the breeding efforts for virus resistance, based on conventional selection and genetic engineering.

A single exposure to an enriched environment stimulates the activation of discrete neuronal populations in the brain of the fos-tau-lacZ mouse.

Storage of experience, including learning and memory, is thought to involve plasticity within pre-existing brain circuits. One model for looking at experience-dependent changes is environmental enrichment (EE), which involves exposing animals to a complex novel environment. Animals exposed to EE have previously been shown to exhibit a variety of behavioural and structural alterations in the brain, including decreased stress, improved learning and memory, altered levels of immediate early genes and synaptic change in the visual cortex. We were interested in understanding what regions of the brain are activated during the initial stages of EE. We used fos-tau-lacZ (FTL) transgenic mice to examine changes in functional activation throughout the brain after a single exposure to EE. We found that there was a significant increase in FTL expression within particular morphologically identified neurons in a series of brain regions in the enriched group compared to control groups, indicating that multiple circuits were activated. These regions include the claustrum, infralimbic cortex, hippocampus, amygdala and the hypothalamus. The data suggest that EE stimulates an initial strong increase in activation of multiple functional circuits. These circuits are presumably involved in the initial response of the animal to the enriched environment.

Clinical efficacy of lorazepam in prophylaxis of anticipatory, acute, and delayed nausea and vomiting induced by high doses of cisplatin. A prospective randomized trial.

Nausea and vomiting are extremely common and most distressing side effects of high-dose cisplatin therapy. Cisplatin induces anticipatory and acute, as well as, delayed emesis. High doses of metoclopramide can effectively decrease the intensity of these symptoms in up to 70% of cases. Several agents, including dexamethasone and antihistamines have been demonstrated to either increase the efficacy of metoclopramide or decrease the side effects. Lorazepam, a benzodiazepine, has both antiemetic and anxiolytic properties. It can be useful as an adjunct to metoclopramide-based therapy. We conducted a randomized trial to evaluate the efficacy of lorazepam in managing anticipatory, acute, and delayed emesis induced by high doses of cisplatin. A total of 180 events involving cisplatin administration (100 mg/m2 as a 24-hour continuous infusion) were randomized to receive metoclopramide along with dexamethasone and clemastine with and without lorazepam. Categorical scales were utilized to document the incidence of nausea and vomiting and side effects related to antiemetic therapy. All episodes are evaluable. Lorazepam significantly reduced the incidence of anticipatory nausea and vomiting (P < .05) as well as acute emesis (P = .05) induced by cisplatin. Delayed emesis was also decreased; however, it was statistically significant on day 3 only (P < .05). Side effects were few except for mild sedation and amnesia, which were significantly more common in those receiving lorazepam (P < .001). We conclude that lorazepam increases the efficacy of metoclopramide against cisplatin-induced anticipatory, acute, and delayed nausea and vomiting. This four-drug regimen may offer one of the best combinations to be utilized in comparative trials against the newly introduced serotonin antagonists.