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Background Multiple sclerosis (MS) is frequently diagnosed in people of reproductive age, many of whom will become pregnant following diagnosis. Although many women report an improvement in symptoms and relapses during pregnancy, symptoms such as fatigue and spasticity are commonly reported and can worsen. Prescribing medications during pregnancy and breastfeeding presents unique challenges and guidance on the use of symptomatic therapies is limited. Objectives This paper aims to provide a consensus on the current evidence base to facilitate informed decision-making and optimise pre-conception counselling. Methods A list of most commonly prescribed medications for symptom management in MS was created using pregnancy and MS-related READ codes in the Welsh GP Dataset, followed by a review by MS neurologists. Results A final list of 24 medications was generated for review. Searches were performed on each medication, and evidence graded using standardised criteria. Evidence-based recommendations were developed and distributed to experts in the field and revised according to feedback using modified Delphi criteria. Conclusions Our guidelines provide evidence-based recommendations on the safety of symptomatic therapies during pregnancy and breastfeeding for general practitioners and specialist teams working with people with MS who are hoping to embark on pregnancy or are currently pregnant. Individual risk–benefit ratios should be considered during pre-conception counselling to optimise symptom burden and minimise harm to both parent and child.

Background: Prevalence of overweight, obesity among children age in Egypt and severe obesity among of all age groups varies very high, children's obesity is an alarming issue. Continually rising prevalence of obesity and overweight in children is a major public health concern. This is due to its various and serious health hazards on one side and its preventable nature on the other side. The problem primarily relies on the ability of parents to recognize their child's overweight/obesity, and to be aware that obesity is a risk factor for long-term health issues. Several studies showed that many parents are not concerned about their children's body weight, because they either think too little of their child's body weight or believe that obesity is inherited, thus modifiable. Parent's perception of child feeding is one of the influencing causes that contribute to child weight status. Although the prevalence of childhood obesity has increased significantly in Egypt, parents are unable to appreciate obesity in their child. Parental beliefs and practices in children’s nutrition may determine deviations in the acquisition of the child’s food preferences and in their self-regulation, who can influence their nutritional status. Childhood obesity and metabolic complications related thereto emerge as a challenge to global health in the 21st century, given its dramatic increase in the last decade in most countries Aim of the study: to assess of parental beliefs and practices about child feeding and its impact on child weight. Setting: The research was conducted on sample of parents (mother, father, children), living in some regions at Menoufia Governorate, Egypt.

The work reported herein describes the synthesis of a new series of anti-inflammatory pyrazolyl thiazolones. In addition to COX-2/15-LOX inhibition, these hybrids exerted their anti-inflammatory actions through novel mechanisms. The most active compounds possessed COX-2 inhibitory activities comparable to celecoxib (IC50 values of 0.09–0.14 µM) with significant 15-LOX inhibitory activities (IC50s 1.96 to 3.52 µM). Upon investigation of their in vivo anti-inflammatory activities and ulcerogenic profiles, these compounds showed activity patterns equivalent or more superior to diclofenac and/or celecoxib. Intriguingly, the most active compounds were more effective than diclofenac in suppressing monocyte-to-macrophage differentiation and inflammatory cytokine production by activated macrophages, as well as their ability to induce macrophage apoptosis. The latter finding potentially adds a new dimension to the previously reported anti-inflammatory mechanisms of similar compounds. These compounds were effectively docked into COX-2 and 15-LOX active sites. Also, in silico predictions confirmed the appropriateness of these compounds as drug-like candidates.

Background. The incidence of type 2 diabetes mellitus (T2DM) has increased over the past years and early identification and management of its complications especially diabetic kidney disease (DKD) is of great importance. T2DM and DKD are of multifactorial etiology with contribution of genetic and environmental factors. We aimed to study the expression of ABCC8 and Notch 2 genes in patients with T2DM and to find their association with DKD. Methods. The present work was carried on 80 patients with T2DM (40 with DKD and 40 without DKD) and 40 healthy subjects as a control group. Real time polymerase chain reaction was used to assess gene expression. Results. Altered expression of ABCC8 and Notch 2 genes were found in patients with T2DM compared to control group. ABCC8 expression had significant positive correlation with HbA1c while Notch 2 expression had significant positive correlation with fasting plasma glucose and HbA1c. Notch 2 expression was significantly higher in patients with DKD compared to those without DKD. Multivariate regression analysis showed that Notch 2 expression had independent relation with increased urinary albumin excretion and reduced estimated glomerular filtration rate. ABCC8 gene expression did not show significant difference between diabetic patients with DKD compared to those without DKD. Conclusion. Increased expression of ABCC8 and Notch 2 genes may play a role in pathogenesis of T2DM. Overexpression of Notch 2 gene may have a role in the development of albuminuria and DKD in patients with T2DM which may represent a possible diagnostic tool and a possible therapeutic target.

Background: Treatment with natalizumab once every 4 weeks is approved for patients with relapsing-remitting multiple sclerosis, but is associated with a risk of progressive multifocal leukoencephalopathy. Switching to extended-interval dosing is associated with lower progressive multifocal leukoencephalopathy risk, but the efficacy of this approach is unclear. We aimed to assess the safety and efficacy of natalizumab once every 6 weeks compared with once every 4 weeks in patients with relapsing-remitting multiple sclerosis. Methods: We did a randomised, controlled, open-label, phase 3b trial (NOVA) at 89 multiple sclerosis centres across 11 countries in the Americas, Europe, and Western Pacific. Included participants were aged 18–60 years with relapsing-remitting multiple sclerosis and had been treated with intravenous natalizumab 300 mg once every 4 weeks with no relapses for at least 12 months before randomisation, with no missed doses in the previous 3 months. Participants were randomly assigned (1:1), using a randomisation sequence generated by the study funder and contract personnel with interactive response technology, to switch to natalizumab once every 6 weeks or continue with once every 4 weeks. The centralised MRI reader, independent neurology evaluation committee, site examining neurologists, site backup examining neurologists, and site examining technicians were masked to study group assignments. The primary endpoint was the number of new or newly enlarging T2 hyperintense lesions at week 72, assessed in all participants who received at least one dose of assigned treatment and had at least one postbaseline MRI, relapse, or neurological examination or efficacy assessment. Missing primary endpoint data were handled under prespecified primary and secondary estimands: the primary estimand included all data, regardless of whether participants remained on the assigned treatment; the secondary estimand classed all data obtained after treatment discontinuation or study withdrawal as missing. Safety was assessed in all participants who received at least one dose of study treatment. Study enrolment is closed and an open-label extension study is ongoing. This study is registered with EudraCT, 2018-002145-11, and ClinicalTrials.gov, NCT03689972. Findings: Between Dec 26, 2018, and Aug 30, 2019, 605 patients were assessed for eligibility and 499 were enrolled and assigned to receive natalizumab once every 6 weeks (n=251) or once every 4 weeks (n=248). After prespecified adjustments for missing data, mean numbers of new or newly enlarging T2 hyperintense lesions at week 72 were 0·20 (95% CI 0·07–0·63) in the once every 6 weeks group and 0·05 (0·01–0·22) in the once every 4 weeks group (mean lesion ratio 4·24 [95% CI 0·86–20·85]; p=0·076) under the primary estimand, and 0·31 (95% CI 0·12–0·82) and 0·06 (0·01–0·31; mean lesion ratio 4·93 [95% CI 1·05–23·20]; p=0·044) under the secondary estimand. Two participants in the once every 6 weeks group with extreme new or newly enlarging T2 hyperintense lesion numbers (≥25) contributed most of the excess lesions. Adverse events occurred in 194 (78%) of 250 participants in the once every 6 weeks group and 190 (77%) of 247 in the once every 4 weeks group, and serious adverse events occurred in 17 (7%) and 17 (7%), respectively. No deaths were reported. There was one case of asymptomatic progressive multifocal leukoencephalopathy (without clinical signs) in the once every 6 weeks group, and no cases in the once every 4 weeks group; 6 months after diagnosis, the participant was without increased disability and remained classified as asymptomatic. Interpretation: We found a numerical difference in the mean number of new or newly enlarging T2 hyperintense lesions at week 72 between the once every 6 weeks and once every 4 weeks groups, which reached significance under the secondary estimand, but interpretation of statistical differences (or absence thereof) is limited because disease activity in the once every 4 weeks group was lower than expected. The safety profiles of natalizumab once every 6 weeks and once every 4 weeks were similar. Although this trial was not powered to assess differences in risk of progressive multifocal leukoencephalopathy, the occurrence of the (asymptomatic) case underscores the importance of monitoring and risk factor consideration in all patients receiving natalizumab. Funding: Biogen.

Purpose of review In this review, we summarize the recently published literature that demonstrates the efficacy and safety of autologous haematopoietic stem cell therapy (AHSCT) in multiple sclerosis (MS) and highlight the importance of supportive care required for the safe and well-tolerated delivery of AHSCT. Recent findings MS is an autoimmune inflammatory and degenerative disorder of the central nervous system (CNS). In the majority of patients, the illness runs a relapsing remitting course (RRMS), culminating in a secondary progressive phase with gradual accumulation of fixed disabilities. Currently available disease-modifying therapies suppress CNS inflammation but have a limited effect on preventing disease progression for which there remains no effective therapy. Over the last two decades, there has been increasing evidence that AHSCT is a highly effective therapeutic strategy for treatment-resistant inflammatory types of MS, especially RRMS. Concerns about the safety of AHSCT in MS, usually a nonlife-threatening disease, have previously limited its use. However, AHSCT can now be delivered safely with major long-term benefits because of increasing transplant centre experience, judicious patient selection and good supportive care. Summary MS is currently the fastest growing indication for AHSCT in Europe. Supportive care before, during and after the transplant period is key to the successful delivery of AHSCT.

In search for effective multi-targeting drug ligands (MTDLs) to address low-grade inflammatory changes of metabolic disorders, we rationally designed some novel glitazones-like compounds. This was achieved by incorporating prominent pharmacophoric motifs from previously reported COX-2, 15-LOX and PPARγ ligands. Challenging our design with pre-synthetic docking experiments on PPARγ showed encouraging results. In vitro tests have identified 4 compounds as simultaneous partial PPARγ agonist, potent COX-2 antagonist (nanomolar IC50 values) and moderate 15-LOX inhibitor (micromolar IC50 values). We envisioned such outcome as a prototypical balanced modulation of the 3 inflammatory targets. In vitro glucose uptake assay defined six compounds as insulin-sensitive and the other two as insulin-independent glucose uptake enhancers. Also, they were able to induce PPARγ nuclear translocation in immunohistochemical analysis. Their anti-inflammatory potential has been translated to effective inhibition of monocyte to macrophage differentiation, suppression of LPS-induced inflammatory cytokine production in macrophages, as well as significant in vivo anti-inflammatory activity. Ligand co-crystallized PPARγ X-ray of one of MTDLs has identified new clues that could serve as structural basis for its partial agonism. Docking of the most active compounds into COX-2 and 15-LOX active sites, pinpointed favorable binding patterns, similar to those of the co-crystallized ligands. Finally, in silico assessment of pharmacokinetics, physicochemical properties, drug-likeness and ligand efficiency indices was performed. Hence, we anticipate that the prominent biological profile of such series will rationalize relevant anti-inflammatory drug development endeavors.

Background and aims: Type 2 diabetes mellitus (T2DM) is a chronic disease with many dramatic complications. It has also been suggested that altered intestinal microbiota leads to increased intestinal permeability and mucosal immune response, contributing to the development of diabetes. We aimed to investigate the effect of introduction of probiotic products on glycemic control and inflammatory markers among patients with T2DM. Methods: the present work was carried on 150 patients with T2DM. The studied patients were subjected to full history taking, clinical examination and laboratory investigations including fasting blood glucose (FBG), 2 hours post prandial blood glucose (2hpp), glycated hemoglobin (HbA1c), total cholesterol (TC), triglycerides (TG), HDL-C, LDL-C, C-reactive protein (CRP), interleukin 6 (IL6) and tumor necrosis factor alpha (TNF α). They were divided into 3 groups each of 50 patients, they were all instructed to eat well balanced diet. The first group was instructed to eat the well balanced diet only, the second group received 2 cups of yogurt daily in addition to diet and the third group received one teaspoonful yeast daily in addition to diet. The effect of the intervention was evaluated after 16 weeks. Results: Patients receiving yogurt and the patients receiving yeast showed significant reduction of FBG,HbA1c, IL6, TNF α, CRP and significant elevation of HDL-C compared to patients on diet only. The 3 groups showed significant reduction in 2hpp blood glucose and LDL-C. Conclusion: Probiotic intake in patients with T2DM has beneficial effect on glycemic control, lipid profile and inflammatory markers after 16 weeks.

Background. The aim of this study is to evaluate the metabolic effects of Ramadan fasting on patients with type 2 diabetes, and their relation to glycemic control, risk of hypoglycemia, as well as any possible effects on diabetic complications. Methods. 300 subjects with type 2 diabetes were assessed to evaluate the metabolic effects of Ramadan fasting regarding glycemic control, risk of hypoglycemia and any possible effects on diabetic complications. The examination included measurement of body mass index (BMI), blood pressure, examination of the foot for sensory loss and peripheral vascular disease (PVD) by assessing the vibration sense and calculating the ankle-brachial index (ABI) respectively. Laboratory tests included fasting plasma glucose (FPG), HbA1c, complete lipid profile, serum creatinine, urinary albumin-to-creatinine ratio (UACR) and calculation of eGFR. Results. BMI, blood pressure, FPG, and triglycerides levels were lower in patients after Ramadan compared to their levels before Ramadan, while eGFR was higher after Ramadan than it was before Ramadan. Hypo-glycemia was highest in patients treated with insulin followed by those treated with oral agents including sulfonylureas as compared to oral agents excluding sulfonylureas (p = 0.002). Conclusion. Fasting during Ramadan can affect body weight, blood pressure, glycemic parameters and the frequency of acute glycemic complications in patients with type 2 diabetes. Hypoglycemia was highest in patients treated with insulin followed by those treated with oral agents especially sulfonylureas.

BackgroundRemote ischaemic preconditioning (RIPC) is the exposure of body parts to brief periods of circulatory occlusion and reperfusion. Recent studies have also shown that RIPC can improve exercise performance in healthy individuals.ObjectiveThis study aimed to assess the effect of RIPC on walking in people with multiple sclerosis (MS).MethodsThis was a double-blind randomised controlled clinical trial. We used three cycles of RIPC delivered by occluding the upper arm with a blood pressure (BP) cuff inflated to a pressure of 30 mm Hg above the systolic BP. In patients in the sham intervention group, the BP cuff was inflated only to 30 mm Hg below diastolic BP. Outcome measures included the Six-Minute Walk Test (6MWT), gait speed, the Borg rate of perceived exertion (RPE) scale, the tolerability of the RIPC using a Numerical Rating Scale for discomfort from 0 to 10, and adverse events. We identified responders meeting the minimal clinically important difference (MCID) established in the literature in each group.ResultsSeventy-five participants completed the study (RIPC: 38 and Sham: 37). The distance walked during the 6MWT improved by 1.9% in the sham group and 5.7% in the RIPC group (p=0.012). The number of responders meeting MCID criteria in the RIPC group was significantly greater compared with the sham intervention group. No serious adverse events occurred.ConclusionSingle cycle of RIPC resulted in immediate improvement in walking distances during 6MWT in people with MS.Trial registration numbersNCT03153553

Background: Fluid and electrolyte balance are critical for the maintenance of life and homeostasis. Therefore, the aim of this study was to evaluate nurses’ knowledge and practice in maintaining fluid and electrolyte balance. Methods: Quasi-experimental design [pre, post, and follow-up tests] was utilized to fulfill the purpose of the study. Settings: This study was conducted at Pediatric Intensive Care Units, Menoufia Governorate, Egypt. Sample: A convenient sample of fifty nurses was represented in this study from January to August 2021. Two tools were used for collecting data. First tool: Fluid balance monitoring questionnaire consisted of two parts to assess nurses' knowledge regarding fluid and electrolyte balance and the second tool: Fluid balance monitoring audit to assess nurses’ practice of fluid balance monitoring. Results: The mean age and standard deviations of studied nurses were 28±6.9 and 34% of them were aged between 25 and 30 years old. Half of the study sample [50%] had a bachelor’s degree. On the pre-test, there were moderately adequate knowledge and incompetent practices of fluid balance monitoring. In conclusion: The study revealed that implementation of a health education program has a positive outcome on the advance of nurses’ knowledge and practices about fluid measurement and maintenance. Recommendation: Ongoing in-service education programs must be implemented at Intensive Care Units in order to boost nurses’ knowledge, practice, and outcome.

TB continues to be a leading health threat despite the availability of powerful anti-TB drugs. We report herein the design and synthesis of various hybrid molecules comprising pyrazine scaffold and various formerly identified anti-mycobacterial moieties. Thirty-one compounds were screened in vitro for their activity against Mycobacterium Tuberculosis H37Rv strain using MABA assay. The results revealed that six compounds (8a, 8b, 8c, 8d, 14b and 18) displayed significant activity against Mtb with MIC values ≤ 6.25 µg/ml versus 6.25 µg/ml for pyrazinamide. The most active compounds were then assessed for their in vitro cytotoxicity against PBMC normal cell line using MTT assay and showed SI > 200. Several in silico studies have been carried out for target fishing of the novel compounds such as shape-based similarity, pharmacophore mapping and inverse docking. Based on this multi-step target fishing study, we suggest that pantothenate synthetase could be the possible target responsible for the action of these compounds. The most active compounds were then successfully docked into the active site of pantothenate synthetase enzyme with favorable binding interactions. In addition, in silico prediction of physicochemical, ADMET and drug-like properties were also determined indicating that compounds 8b, 8c and 8d are promising candidates for the development of new anti-TB agents with enhanced activity and better safety profile.

Intravenous recombinant tissue-plasminogen-activator (rtPA) and mechanical-thrombectomy (MT) are currently the only approved treatments for acute ischemic stroke. Their effectiveness was demonstrated in several clinical trials, and is therefore standard of care. Pregnant women were not included in these studies and consequently the effectiveness and safety in this group are unclear. We present a rare case of a patient in the third-trimester of pregnancy that underwent MT. A 29-year-old woman of 39 weeks' gestation presented with left facial-paresis, hemiparesis, and neglect. Her CT-Angiogram showed a large occlusive thrombus within the right M1-M2 segments. During pregnancy she had developed thrombocytopenia. There was initial treatment decision dilemma. In view of her history of thrombocytopenia, there was concern about administering rtPA due to the risk of bleeding. As the thrombus was large, rtPA may also be ineffective. MT was proposed by the Stroke Physician as the preferred treatment option. A concern from the Interventional-Radiologist was the risk of exposure to radiation and contrast agents. As the patient had a disabling stroke at a young age, decision was made to proceed with MT which started 141 minutes after symptom onset. The clot was aspirated without complications. Final check angiogram showed complete resolution of flow within the right middle cerebral artery territory. The patient underwent elective uncomplicated Caesarean-section 5 days later delivering a healthy new born. Severe stroke in pregnancy is rare, but has grave consequences for both mother and infant. Timely decision-making is crucial. Our case demonstrates that MT can be provided safely and effectively in the third trimester of pregnancy.

A series of novel 1,4,6-trisubstituted-2-oxo-1,2-dihydropyridine-3-carbonitriles supported with some functionalities reported to contribute to significant chemotherapeutic potential were synthesized and evaluated for their antimicrobial and/or cytotoxic activities. Thirteen compounds exhibited cytotoxic potential against a panel of three human tumor cell lines. Compounds 15, 23, and 24 proved to be the most active agents with a broad spectrum of cytotoxic activity. Analog 24 was considered as the most active cytotoxic agent, being 2.5 times more active than doxorubicin against the colon HT29 carcinoma cell line. Seventeen compounds were able to exert a variable antimicrobial profile, among which analogs 15, 20, 21, 23, and 24 were prominently active. The highest antimicrobial potential was displayed by analog 24, being equipotent to ampicillin against Staphylococcus aureus and Escherichia coli, together with a considerable antifungal activity comparable with clotrimazole. Collectively, compounds 15, 23, and 24 could be considered as possible dual antimicrobial-anticancer candidates.

A highly selective and sensitive fluorescence assay for kanamycin has been developed that depends on complementation of two splits of DNA aptamer. One DNA split was labeled with CuS nanoparticle and the other was decorated with biotin, which enabled coupling with streptavidin magnesphere paramagnetic particles (PMPs). Complementation of the two-aptamer splits happened only in the presence of kanamycin and the subsequent sandwich was separated via a magnet. The released Cu(II) was reduced to Cu(I) by sodium ascorbate and finally catalyzed the click reaction between fluorogenic 3-azido-7-hydroxycoumarin and propargyl alcohol to afford the corresponding fluorescent 1,4-disubstituted-1,2,3-triazole. The fluorescence signal produced (λex. = 365 nm, λem. = 470 nm) was dependent on kanamycin concentration. Fluorescence signal amplification was found to be in good linear relationship with the logarithm of kanamycin concentration in the range of 0.04-20 nM. Furthermore, the proposed assay showed a good reproducibility, high selectivity and low detection limits for kanamycin determination. In addition, the capability of the proposed method to detect kanamycin in biological samples with satisfactory results was demonstrated.

Click chemistry was used to synthesize a new series of thioquinazolinone molecules equipped with propargyl moiety,1,2,3-triazolyl and isoxazolyl rings. Our design was based on merging pharmacophores previously reported to exhibit COX-2 inhibitory activities to a thioquinazolinone-privileged scaffold. The synthesized compounds were subjected to in vitro cyclooxygenase COX-1/COX-2 and 15-LOX inhibition assays. Compounds 2c, 3b, 3h, 3j, and 3k showed COX-2 inhibition with IC50 (μM) 0.18, 0.19, 0.11, 0.16 and 0.17 respectively. These values were compared to celecoxib (IC50 0.05 μM), diclofenac (IC50 0.8 μM) and indomethacin (IC50 0.49 μM) reference drugs. They also showed 15-LOX inhibition with IC50 (μM) 6.21, 4.33, 7.62, 5.21 and 3.98 respectively. These values were compared with Zileuton (IC50 2.41 μM) and Meclofenamate sodium (IC50 5.64 μM) as positive controls. These compounds were further challenged by PMA-induced THP-1 differentiation assay where compounds 2c and 3j inhibited monocyte to macrophage differentiation efficiently with IC50 values of 4.78 μM and 5.63 μM, respectively, compared to that of diclofenac sodium (4.86 μM). On the other hand, 3h demonstrated a significantly increased potency compared to diclofenac in this assay (IC50 = 0.13 μM). The same compounds exhibited significant in vivo anti-inflammatory effect as indicated by the formalin-induced rat-paw edema test. Docking experiments of compounds 2c, 3b, 3h, 3j, and 3k into COX-2 binding pocket have been conducted, where strong binding interactions have been identified and effective overall docking scores have been recorded. Their drug-likeness has been assessed using Molinspiration, Molsoft and Pre-ADMET software products.

Background Rosemary (Rosmarinus officinalis L.) is a spice and medicinal herb widely used around the world of the natural antioxidants, and it has been widely accepted as one of the spices with the highest antioxidant activity. Transglutaminase (EC 2.3.2.13: TGase) is an enzyme capable of catalysing acyl transfer reactions by introducing covalent cross-links between proteins, as well as peptides and various primary amines. TGase activity in plants was first observed in pea seedlings, and subsequently found in organs of both lower and higher plants. Recently. TGase has captured researchers' interest due to its attractive potential application in food industries. Therefore, the objectives of this study are isolation and purification of TGase from new plant source rosemary (Rosmarinus officinalis L.) leaves at the laboratory scale. Moreover, investigation of the biochemical properties of the purified TGase to provide a suitable TGase enzyme for food industry applications are in focus. Material and methods Rosemary (Rosmarinus officinalis L.) leaves was used as a new plant source to TGase. The biochemical characteristics of the crude and purified enzyme were determined. Results Rosemary (Rosmarinus officinalis L.) TGase was purified to homogeneity by successive three purification steps including ammonium sulfate precipitatation, ion exchange chromatography on DEAE-Sephadex A-50 column and Size exclusion column chromatography on Sephadex G-100 column. Under experimental conditions. 20-30% of ammonium sulfate saturation in the enzyme solution had a high yield of enzyme activity could be obtained. The purified enzyme from the Sephadex G-100 column had 21.35% yield with increased about 7.31 in purification fold. Rosemary TGase exhibited optimum activity at pH 7.0 and 55°C for the catalytic reaction of hydroxylarnine and Z-Gln-Gly. The purified TGase almost maintained full activity after incubation for 15 ruin up to 60°C and it was completely inactivated at 85°C. The rosemary TGase was stimulated at 2-6 rnM CaCl2 concentrations while it lost about 5-20% from its activity by increasing CaCl2 concentration. Sodium chloride (2-14%) shows no noticeable inhibition of the purified TGase activity. Mg+2, Ba+2 were acivited by the purified TGase while it was str ongly inhibited by Fe+2, moderately by Cir2 and Mn+2. Conclusion This paper reports on the purification and characterisation of TGase from newly isolated plant, rosemary (Rosmarinus officinalis L.) leaves. Finding results of the TGase properties make this enzyme a good candidate for application in the food industry. However, additional work is required to increase activity yield during extraction and purification for commercial scale of TGase from this plant.

Background Crossover in the pathogenic mechanisms of amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS) has been described but is poorly understood. A GGGGCC hexanucleotide repeat expansion of C9ORF72 has recently been identified in a significant proportion of patients with ALS. Methods In approximately 650 patients diagnosed with ALS from the North of England we identified seven patients who initially presented with MS. DNA obtained from five patients with MS-ALS and 215 patients with MS alone was screened for the C9ORF72 expansion. Post-mortem material was examined from two patients with MS-ALS. Gene expression profiling was performed on lymphoblastoid cells and levels of CXCL10 were measured in cerebrospinal fluid (CSF) from patients with ALS with and without the C9ORF72 expansion and controls. Results Concurrence of MS and ALS is higher than expected in our population. The C9ORF72 expansion was identified in 80% of patients with MS-ALS but not in those with MS alone. In the presence of preceding MS, C9ORF72 -ALS was more rapidly progressive. MetaCore analysis identified alteration of the NF-кB pathway in C9ORF72 -ALS and non- C9ORF72 -ALS. NF-кB activation is associated with increased expression of the neuroprotective cytokine CXCL10 but, in C9ORF72 -ALS, CXCL10 is downregulated and CSF levels are reduced. Conclusions We propose that MS-associated neuroinflammation may affect penetrance and progression of the C9ORF72 expansion. In particular, the NF-кB pathway is activated in MS and appears to be dysfunctional in C9ORF72 -ALS. Aberrant downregulation of CXCL10 may explain the predisposition of C9ORF72 expansion carriers to develop ALS in the context of MS and NF-кB activation, and offers a potential therapeutic target.

Background: Enzymes of the Glutathione S-transferase system (GST) modulate the effects of exposure to several cytotoxic and genotoxic agents. Nitric oxide (NO) is constitutively synthesized in the endothelium by endothelial nitric oxide synthase (eNOS) and acts as a pleiotropic regulator involved in carcinogenesis. Vitamin D levelsmay influence breast cancer development. The vitamin D receptor(VDR) is a crucial mediator for the cellular effects of vitaminD and additionally interacts with other cell-signaling pathwaysthat influence cancer development. Objectives: To check for the association of polymorphisms of GST, eNOS3 and VDR genes with the susceptibility and severity of breast cancer in Egyptian cases. Subjects: This work included 100 cases with breast cancer and 100 healthy individuals. The mean age of cases was 48.31±11.40 years. They included 100 females. Methods: DNA was amplified using PCR-RFLP for detection of polymorphisms related to eNOS3 and VDR , also DNA was amplified using PCR-SSP for detection of polymorphisms related to GST and calculating the odds ratios and their 95% confidence intervals. Results: Total cases showed high significant frequency of eNOS3-786 CC (P

Type 1 diabetes (T1D) is a genetically conditioned autoimmune disease in which cytokines play an important role. Objectives. To check for the association of polymorphisms of cytokine genes with type 1 diabetes. Subjects. This work included 50 cases with T1D and 98 healthy individuals from the Nile Delta region of Egypt. Cases included 20 males and 30 females with a median age of 25 and range of 15-50 years.DNA was amplified using PCR with sequence-specific primers for detection of polymorphisms related to tumor necrosis factor (TNF)-alpha(- 308) (G/A), interleukin (IL)-10(- 1082) (G/A), IL-6(- 174) (G/C), and IL-1Ra (VNTR).Cases with T1D showed significant higher frequency of genotypes of TNF-alpha(- 308) AA (p0.001, odds ratio (OR) = 7.91), IL-6-17CC (p0.05, OR = 3.36) and IL-1Ra A1A1 (p0.05, OR = 3.68) with significant lower frequencies of TNF-alpha(- 308) GA, and IL-1Ra A1A2 genotypes (p0.001 and0.05, respectively). They also showed significant higher frequency of TNF-alpha(- 308) allele A (p0.05, OR = 2.0), IL-1Ra allele A1 (p0.05, OR = 2.98) with a significant lower frequency of TNF-alpha(- 308) G allele and IL-1Ra A2 allele (p0.05). No significant difference was detected among cases in relation to IL-10(- 1082) (G/A) genotypes or alleles nor in relation to age, sex, consanguinity or family history of the disease.Polymorphisms related to TNF-alpha and IL-1Ra genes may be considered genetic markers for T1D among Egyptians with a potential impact on family counseling and management.

Brachial plexus neuritis in the presence of herpes zoster infection is uncommon. Motor involvement is probably due to the spreading of inflammation from the dorsal root ganglia to the ventral roots and may be more extensive than the affected dermatomes. We present a case of herpes zoster brachial plexopathy with pure motor involvement both clinically and electrophysiologically.

Excitatory transmission in the brain is commonly mediated by the α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors. In amyotrophic lateral sclerosis (ALS), AMPA receptors allow cytotoxic levels of calcium into neurons, contributing to motor neuron injury. We have previously shown that oculomotor neurons resistant to the disease process in ALS show reduced AMPA-mediated inward calcium currents compared with vulnerable spinal motor neurons. We have also shown that PTEN (phosphatase and tensin homolog deleted on chromosome 10) knockdown via siRNA promotes motor neuron survival in models of spinal muscular atrophy (SMA) and ALS. It has been reported that inhibition of PTEN attenuates the death of hippocampal neurons post injury by decreasing the effective translocation of the GluR2 subunit into the membrane. In addition, leptin can regulate AMPA receptor trafficking via PTEN inhibition. Thus, we speculate that manipulation of AMPA receptors by PTEN may represent a potential therapeutic strategy for neuroprotective intervention in ALS and other neurodegenerative disorders. To this end, the first step is to establish a fibroblast–iPS–motor neuron in vitro cell model to study AMPA receptor manipulation. Here we report that iPS-derived motor neurons from human fibroblasts express AMPA receptors. PTEN depletion decreases AMPA receptor expression and AMPA-mediated whole-cell currents, resulting in inhibition of AMPA-induced neuronal death in primary cultured and iPS-derived motor neurons. Taken together, our results imply that PTEN depletion may protect motor neurons by inhibition of excitatory transmission that represents a therapeutic strategy of potential benefit for the amelioration of excitotoxicity in ALS and other neurodegenerative disorders.

PTEN (phosphatase and tensin homologue deleted in chromosome 10) was first identified as a candidate tumour suppressor gene located on chromosome 10q23. It is considered as one of the most frequently mutated genes in human malignancies. Emerging evidence shows that the biological function of PTEN extends beyond its tumour suppressor activity. In the central nervous system PTEN is a crucial regulator of neuronal development, neuronal survival, axonal regeneration and synaptic plasticity. Furthermore, PTEN has been linked to the pathogenesis of neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis. Recently increased attention has been focused on PTEN as a potential target for the treatment of brain injury and neurodegeneration. In this review we discuss the essential functions of PTEN in the central nervous system and its involvement in neurodegeneration.

Th17 cells are a highly pro-inflammatory T-helper cell subset characterised by the expression of IL17. They have been implicated in a variety of allergic and autoimmune conditions. T-regulatory (Treg) cells, a subset of CD4 cells which express Foxp3, CD25, IL10 and TGFβ, can suppress the activity of Th17 cells. In this study, we show that the circulating levels of Th17 and Treg cells in peripheral blood are correlated; furthermore, the expression of the pro-inflammatory cytokine IL17 and the anti-inflammatory cytokine IL10 by CD4 cells are also correlated. However, we found no clear correlation between cerebrospinal fluid (CSF) IL10 and IL17 cytokine levels in MS, approaching a negative correlation at the time of relapse, and an overall negative correlation between CSF IL17 and TGFβ levels, suggesting a lack of central regulation of pro:anti-inflammatory balance in this demyelinating condition.

The aim of this study was to confirm if there is a link between the alteration in blood levels of trace elements (chromium, copper, lead, cadmium, and zinc) and dehydroepiandrosterone sulfate (DHEAS) in healthy and diabetic states. This study is the first study to test these parameters in Egyptians. The study included 150 subjects divided into the following four groups: healthy middle-aged, healthy elderly, middle-aged diabetics, and elderly diabetics. Our results revealed a statistically significant decrease in the level of DHEAS in the elderly compared to middle-aged healthy and diabetic groups (p < 0.05). There was a significant difference between the middle-aged groups with respect to zinc, copper, chromium, and cadmium levels. Zinc and copper were lower in the diabetic subjects while chromium and cadmium were higher in the same group in comparison to healthy subjects. In the elderly groups, there were significant increases in chromium and cadmium levels in diabetic subjects rather than healthy ones. There was a significant increase in the thiobarbituric acid reactive substance level in the elderly healthy and diabetic groups and a significant decrease in the glutathione level in the elderly groups. There was no correlation between the levels of trace elements and DHEAS or between the levels of DHEAS, oxidants, and antioxidants in all of the tested groups. In conclusion, only the DHEAS level was correlated with age. There was no difference between the diabetic and healthy groups with respect to the levels of trace elements, with the exception of chromium and cadmium, which suggests the effect of pollution on the pathogenesis of diabetes in Egyptians. No correlation existed between the levels of DHEAS and trace elements, oxidants, and antioxidants. Finally, we believe that there is a large regional variation in the levels of trace elements due to different environmental exposure and nutritional factors which are responsible for contradictory results regarding the pathogenesis of diseases related to alterations in the levels of trace elements.