Relationship between styrene exposure and prolactin secretion in human and animal studies: A systematic review.

Styrene is widely used in industrial applications. Inhalation exposure occurs in the industry. Some studies indicated that serum prolactin concentrations increased after exposure to styrene, while other studies found no change. In this systematic review, the search was done with the keywords styrene and prolactin in the PubMed, Science Direct, Web of Science and Scopus databases, regardless of the publication period. 118 studies were obtained and only seven articles were finally selected according to exclusion and inclusion criteria. The effect of styrene on prolactin secretion was selected in both human and animal studies. The increased response was seen in inhalation exposures. Subcutaneous exposure has no significant effect on prolactin levels. The observed responses were both dose-dependent and gender-dependent. Changes in serum prolactin were more frequent in women compared to exposed men. Dopamine depletion was not observed in all studies, so more tests on laboratory animals are necessary to clarify the possible mechanism.

Counteracting age-related VEGF signaling insufficiency promotes healthy aging and extends life span.

Aging is an established risk factor for vascular diseases, but vascular aging itself may contribute to the progressive deterioration of organ function. Here, we show in aged mice that vascular endothelial growth factor (VEGF) signaling insufficiency, which is caused by increased production of decoy receptors, may drive physiological aging across multiple organ systems. Increasing VEGF signaling prevented age-associated capillary loss, improved organ perfusion and function, and extended life span. Healthier aging was evidenced by favorable metabolism and body composition and amelioration of aging-associated pathologies including hepatic steatosis, sarcopenia, osteoporosis, "inflammaging" (age-related multiorgan chronic inflammation), and increased tumor burden. These results indicate that VEGF signaling insufficiency affects organ aging in mice and suggest that modulating this pathway may result in increased mammalian life span and improved overall health.

Transformation Foci in IDH1-mutated Gliomas Show STAT3 Phosphorylation and Downregulate the Metabolic Enzyme ETNPPL, a Negative Regulator of Glioma Growth.

IDH1-mutated gliomas are slow-growing brain tumours which progress into high-grade gliomas. The early molecular events causing this progression are ill-defined. Previous studies revealed that 20% of these tumours already have transformation foci. These foci offer opportunities to better understand malignant progression. We used immunohistochemistry and high throughput RNA profiling to characterize foci cells. These have higher pSTAT3 staining revealing activation of JAK/STAT signaling. They downregulate RNAs involved in Wnt signaling (DAAM2, SFRP2), EGFR signaling (MLC1), cytoskeleton and cell-cell communication (EZR, GJA1). In addition, foci cells show reduced levels of RNA coding for Ethanolamine-Phosphate Phospho-Lyase (ETNPPL/AGXT2L1), a lipid metabolism enzyme. ETNPPL is involved in the catabolism of phosphoethanolamine implicated in membrane synthesis. We detected ETNPPL protein in glioma cells as well as in astrocytes in the human brain. Its nuclear localization suggests additional roles for this enzyme. ETNPPL expression is inversely correlated to glioma grade and we found no ETNPPL protein in glioblastomas. Overexpression of ETNPPL reduces the growth of glioma stem cells indicating that this enzyme opposes gliomagenesis. Collectively, these results suggest that a combined alteration in membrane lipid metabolism and STAT3 pathway promotes IDH1-mutated glioma malignant progression.

Cellular and molecular characterization of IDH1-mutated diffuse low grade gliomas reveals tumor heterogeneity and absence of EGFR/PDGFRα activation.

Diffuse low grade gliomas (DLGG, grade II gliomas) are slowly-growing brain tumors that often progress into high grade gliomas. Most tumors have a missense mutation for IDH1 combined with 1p19q codeletion in oligodendrogliomas or ATRX/TP53 mutations in astrocytomas. The phenotype of tumoral cells, their environment and the pathways activated in these tumors are still ill-defined and are mainly based on genomics and transcriptomics analysis. Here we used freshly-resected tumors to accurately characterize the tumoral cell population and their environment. In oligodendrogliomas, cells express the transcription factors MYT1, Nkx2.2, Olig1, Olig2, Sox8, four receptors (EGFR, PDGFRα, LIFR, PTPRZ1) but not the co-receptor NG2 known to be expressed by oligodendrocyte progenitor cells. A variable fraction of cells also express the more mature oligodendrocytic markers NOGO-A and MAG. DLGG cells are also stained for the young-neuron marker doublecortin (Dcx) which is also observed in oligodendrocytic cells in nontumoral human brain. In astrocytomas, MYT1, PDGFRα, PTPRZ1 were less expressed whereas Sox9 was prominent over Sox8. The phenotype of DLGG cells is overall maintained in culture. Phospho-array screening showed the absence of EGFR and PDGFRα phosphorylation in DLGG but revealed the strong activation of p44/42 MAPK/ERK which was present in a fraction of tumoral cells but also in nontumoral cells. These results provide evidence for the existence of close relationships between the cellular phenotype and the mutations found in DLGG. The slow proliferation of these tumors may be associated with the absence of activation of PDGFRα/EGFR receptors.

Efficacy and safety of liraglutide compared to sulphonylurea during Ramadan in patients with type 2 diabetes (LIRA-Ramadan): a randomized trial.

AIMS: Compare effects of liraglutide 1.8 mg and sulphonylurea, both combined with metformin, on glycaemic control in patients with type 2 diabetes (T2D) fasting during Ramadan. MATERIALS AND METHODS: In this up to 33-week, open-label, active-controlled, parallel-group trial, adults [glycated haemoglobin (HbA1c) 7%-10% (53-86 mmol/mol); body mass index ≥20 kg/m(2) ; intent to fast] were randomized (1:1) ≥10 weeks before Ramadan to either switch to once-daily liraglutide (final dose 1.8 mg) or continue pre-trial sulphonylurea at maximum tolerated dose, both with metformin. PRIMARY ENDPOINT: change in fructosamine, a validated marker of short-term glycaemic control, during Ramadan. RESULTS: Similar reductions in fructosamine levels were observed for both groups during Ramadan [liraglutide (-12.8 µmol/L); sulphonylurea (-16.4 µmol/L); estimated treatment difference (ETD) 3.51 µmol/L (95% CI: -5.26; 12.28); p = 0.43], despite lower fructosamine levels in the liraglutide group at start of Ramadan. Fewer documented symptomatic hypoglycaemic episodes were reported in liraglutide-treated (2%, three subjects) versus sulphonylurea-treated patients (11%, 18 subjects). No severe hypoglycaemic episodes were reported by either group. Body weight decreased more during Ramadan with liraglutide (ETD: -0.54 kg; 95% CI: -0.94;-0.14; p = 0.0091). The proportion of patients reporting adverse events was similar between groups. Liraglutide led to greater HbA1c reduction [ETD: -0.59% (-6.40 mmol/mol), 95% CI: -0.79; -0.38%; -8.63; -4.17 mmol/mol; p < 0.0001]. CONCLUSIONS: Despite lower fructosamine levels and body weight at the beginning of Ramadan, use of liraglutide showed similar glycaemic improvements, fewer hypoglycaemic episodes and greater body weight reduction compared with sulphonylurea. LIRA-Ramadan provides evidence for liraglutide being safe and efficacious for management of T2D during Ramadan fasting.

The Safety and Benefit of Statins in Liver Cirrhosis: a Review.

Dyslipidemia is a primary, major risk factor for coronary artery disease CAD. The prevalence of dyslipidemia had decreased over the past 30 years, which may in part be explained by the steady increase in the use of lipid-lowering drug therapy, especially statins. Cardiovascular risk has been shown to be greater in liver disease (20% in the liver cirrhosis vs. 12% in the general population), where statins can play an important role as a primary and secondary prevention for CAD. Given patients with chronic liver disease, especially liver cirrhosis are at risk of decreased hepatic clearance, there is concern that this patient population may be at higher risk for complications from statin therapy. Several retrospective studies showed that statin use in chronic liver disease and cirrhosis is safe, and even it was associated with lower mortality and lower rate of hepatic decompensation. This review discusses the safety and the different mechanisms where statins can decrease the rate of complications in liver cirrhosis, including portal hypertension, sepsis and the incidence of hepatocellular carcinoma.

Genome-wide analysis of the AP2/ERF family in Eucalyptus grandis: an intriguing over-representation of stress-responsive DREB1/CBF genes.

BACKGROUND: The AP2/ERF family includes a large number of developmentally and physiologically important transcription factors sharing an AP2 DNA-binding domain. Among them DREB1/CBF and DREB2 factors are known as master regulators respectively of cold and heat/osmotic stress responses. EXPERIMENTAL APPROACHES: The manual annotation of AP2/ERF family from Eucalyptus grandis, Malus, Populus and Vitis genomes allowed a complete phylogenetic study for comparing the structure of this family in woody species and the model Arabidopsis thaliana. Expression profiles of the whole groups of EgrDREB1 and EgrDREB2 were investigated through RNAseq database survey and RT-qPCR analyses. RESULTS: The structure and the size of the AP2/ERF family show a global conservation for the plant species under comparison. In addition to an expansion of the ERF subfamily, the tree genomes mainly differ with respect to the group representation within the subfamilies. With regard to the E. grandis DREB subfamily, an obvious feature is the presence of 17 DREB1/CBF genes, the maximum reported to date for dicotyledons. In contrast, only six DREB2 have been identified, which is similar to the other plants species under study, except for Malus. All the DREB1/CBF and DREB2 genes from E. grandis are expressed in at least one condition and all are heat-responsive. Regulation by cold and drought depends on the genes but is not specific of one group; DREB1/CBF group is more cold-inducible than DREB2 which is mainly drought responsive. CONCLUSION: These features suggest that the dramatic expansion of the DREB1/CBF group might be related to the adaptation of this evergreen tree to climate changes when it expanded in Australia.

Laryngeal sensory neuropathy in patients with diabetes mellitus.

OBJECTIVE: To determine the prevalence of laryngeal sensory neuropathy in patients with type 2 diabetes mellitus. METHODS: A cross-sectional study was performed, comprising 50 patients diagnosed with type 2 diabetes mellitus and 36 healthy controls. In the diabetic group, glycaemic control level, disease duration and presence of neuropathy were assessed. Participants were diagnosed with laryngeal sensory neuropathy if they had a cough, globus pharyngeus or throat clearing lasting for more than six weeks, in the absence of laryngopharyngeal reflux disease, allergies, asthma, angiotensin-converting enzyme inhibitor intake or psychogenic disorders. RESULTS: In the diabetic group, the mean age ± standard deviation was 44.66 ± 10.07 years. Sixty per cent of patients were male, 42 per cent had had diabetes for more than five years and 52 per cent had average to poor glycaemic control. The prevalence of laryngeal sensory neuropathy was 42 per cent in the diabetic group, compared with 13.9 per cent in controls; this difference was statistically significant (p = 0.005). There was no association between the prevalence of laryngeal sensory neuropathy and glycaemic control level, disease duration or presence of neuropathy. CONCLUSION: Laryngeal sensory neuropathy is more common in patients with type 2 diabetes mellitus than in controls.

Barriers to the delivery of optimal antidiabetic therapy in the Middle East and Africa.

BACKGROUND: The prevalence of type 2 diabetes is increasing worldwide, but developing nations will bear a disproportionate share of this burden. Countries in the Middle East and Africa are in a state of transition, where marked disparities of income and access to education and healthcare exist, and where the relatively young populations are being exposed increasingly to processes of urbanisation and adverse changes in diet that are fuelling the diabetes epidemic. Optimising diabetes care in these nations is crucial, to minimise the future burden of complications of diabetes. METHODS: We have reviewed the barriers to effective diabetes care with special relevance to countries in this region. RESULTS: The effects of antidiabetic treatments themselves are unlikely to differ importantly in the region compared with elsewhere, but economic inequalities within countries restrict access to newer treatments, in particular. Values relating to family life and religion are important modifiers of the physician-patient interaction. Also, a lack of understanding of diabetes and its treatments by both physicians and patients requires more and better diabetes education, delivered by suitably qualified health educators. Finally, sub-optimal processes for delivery of care have contributed to a lack of proper provision of testing and follow-up of patients in many countries. CONCLUSION: Important barriers to the delivery of optimal diabetes care exist in the Middle East and Africa.

Barriers to the delivery of diabetes care in the Middle East and South Africa: a survey of 1,082 practising physicians in five countries.

AIMS: Developing countries face a high and growing burden of type 2 diabetes. We surveyed physicians in a diverse range of countries in the Middle East and Africa (Egypt, Kingdom of Saudi Arabia, United Arab Emirates, South Africa and Lebanon) with regard to their perceptions of barriers to type 2 diabetes care identified as potentially important in the literature and by the authors. METHODS: One thousand and eighty-two physicians completed a questionnaire developed by the authors. RESULTS: Most physicians enrolled in the study employed guideline-driven care; 80-100% of physicians prescribed metformin (with lifestyle intervention, where there are no contraindications) for newly diagnosed type 2 diabetes, with lifestyle intervention alone used where metformin was not prescribed. Sulfonylureas were prescribed widely, consistent with the poor economic status of many patients. About one quarter of physicians were not undertaking any form of continuing medical education, and relatively low proportions of practices had their own diabetes educators, dieticians or diabetic foot specialists. Physicians identified the deficiencies of their patients (unhealthy lifestyles, lack of education and poor diet) as the most important barriers to optimal diabetes care. Low-treatment compliance was not ranked highly. Access to physicians did not appear to be a problem, as most patients were seen multiple times per year. CONCLUSIONS: Physicians in the Middle East and South Africa identified limitations relating to their patients as the main barrier to delivering care for diabetes, without giving high priority to issues relating to processes of care delivery. Further study would be needed to ascertain whether these findings reflect an unduly physician-centred view of their practice. More effective provision of services relating to the prevention of complications and improved lifestyles may be needed.

The effect of parental intellectual disability status on child protection service worker decision making.

BACKGROUND: There is evidence to suggest that parents with an intellectual disability (ID) constitute a higher proportion of child-protective services (CPS) cases than would be expected based on the prevalence of ID in the general population. Researchers have suggested that the stereotypic assumptions and expectations that CPS workers have about parents with an ID might influence decisions and responses made to such parents. This study examined whether parental ID (having an ID vs. not) had an effect on CPS workers' emotional reactions, attributions and decisions about risk to the child, whether to remove the child and workers' general willingness to help the parent. METHOD: Two hundred and twelve CPS workers read vignettes describing parents who were labelled as either having or not having an ID. Workers responded to the vignettes by making ratings of their emotional reactions, attributions and decisions regarding risk, removal and helping. RESULTS: CPS workers made significantly higher ratings of pity, willingness to help and risk for parents with an ID than for parents without an ID. Lower ratings of anger and disgust were found for parents with an ID than for parents without an ID. Parents' intellectual status did not have a direct effect on workers' attributions or removal decisions. CONCLUSIONS: The results show evidence for the influence of stereotypes regarding parental ID due to its differential effect on CPS workers' emotional reactions and decisions about child risk and their willingness to help.

Long-term administration of Silymarin augments proinflammatory mediators in the hippocampus of rats: evidence for antioxidant and pro-oxidant effects.

Silymarin (SMN) is used as an antioxidant complex to attenuate the pro-oxidant effects of toxic agents. This study was designed to investigate the impact of a long-term administration of SMN on proinflammatory mediators, oxidative stress biomarkers and on the levels of interleukin-1ß (IL-1ß) transcript in the hippocampus. A total of 40 adult male Wistar rats were assigned into control and test groups. Animals in the test group were subdivided into four subgroups according to the following treatment profile: carbon tetrachloride (CCl(4), 0.5 ml/kg), SMN 25, SMN 50 and SMN 100 (mg/kg). The animals received the compounds by gastric gavage. Following the 8-week treatment period, animals in the CCl(4) group showed body weight loss, while the test groups except SMN 100 revealed a significant (p < 0.05) positive body weight gain. The levels of nitric oxide (NO) and malondialdehyde (MDA) as pro-oxidant and lipid peroxidation index, respectively, increased in CCl(4)- and SMN 100-treated groups, while SMN at lower dose levels did not alter the NO and MDA content. The concentration of total thiol molecules increased in the SMN 50 group and showed a remarkable decrease in CCl(4) and SMN 100 groups. Animals treated with CCl(4) or SMN 100 showed an upregulation of IL-1ß, while animals in SMN 25 and SMN 50 groups showed a slight downregulation of expression of IL-1ß at the messenger RNA level. These findings suggest that SMN at higher dosage level might exert pro-oxidant effect as an increase in the level of MDA and proinflammatory mediators such as NO, and upregulation of IL-1ß in the hippocampus were shown.

Effect of renal transplantation on visual evoked potential abnormalities of chronic renal failure.

BACKGROUND: Cranial neuropathies including optic nerve involvement are well-known complications of chronic renal failure (CRF), but most clinicians often do not follow the progression of these damages during course of CRF or their reversibility after treatment. So, this study evaluates effects of renal transplantation on visual system functions using visual-evoked potentials (VEP). METHODS AND MATERIALS: Forty CRF transplantation candidates and 40 control healthy persons underwent VEP before transplantation. VEP was repeated 3 months later for patients who had successful grafts. RESULTS: None of recorded VEP changes were significant in our study, although the absolute number of normal parameters increased after transplantation. In patients who had less than 1 year duration of CRF, more positive changes were observed after transplantation (p < .05). CONCLUSION: Our study showed the VEP changes were not significant. This may have been due to the delay in transplantation. CRF duration had a significant effect on almost all parameters of VEP which means that the longer duration of CRF lead to a decreased probability of VEP changes to return to normal after transplantation.

Primary and secondary neoplasms of the spleen.

With the exception of lymphoma involving the spleen, other primary and secondary neoplasms are rare and infrequently encountered. Primary malignant neoplasms involving the spleen are lymphoma and angiosarcoma. Primary benign neoplasms involving the spleen include hemangioma, lymphangioma, littoral cell angioma and splenic cyst and solid lesions such as hamartoma and inflammatory pseudotumor.

Optimising the medical management of hyperglycaemia in type 2 diabetes in the Middle East: pivotal role of metformin.

AIMS: Increases in the prevalence of type 2 diabetes will likely be greater in the Middle East and other developing countries than in most other regions during the coming two decades, placing a heavy burden on regional healthcare resources. METHODOLOGY: Medline search, examination of data from major epidemiological studies in the Middle Eastern countries. RESULTS: The aetiology and pathophysiology of diabetes appears comparable in Middle Eastern and other populations. Lifestyle intervention is key to the management of diabetes in all type 2 diabetes patients, who should be encouraged strongly to diet and exercise. The options for pharmacologic therapy in the management of diabetes have increased recently, particularly the number of potential antidiabetic combinations. Metformin appears to be used less frequently to initiate antidiabetic therapy in the Middle East than in other countries. Available clinical evidence, supported by current guidelines, strongly favours the initiation of antidiabetic therapy with metformin in Middle Eastern type 2 diabetes patients, where no contraindications exist. This is due to its equivalent or greater efficacy relative to other oral antidiabetic treatments, its proven tolerability and safety profiles, its weight neutrality, the lack of clinically significant hypoglycaemia, the demonstration of cardiovascular protection for metformin relative to diet in the UK Prospective Diabetes Study and in observational studies, and its low cost. Additional treatments should be added to metformin and lifestyle intervention as diabetes progresses, until patients are receiving an intensive insulin regimen with or without additional oral agents. CONCLUSIONS: The current evidence base strongly favours the initiation of antidiabetic therapy with metformin, where no contraindications exist. However, metformin may be under-prescribed in the Middle East.

Safety of low-dose cyclosporine therapy before transplantation in kidney allograft recipients.

INTRODUCTION: Graft dysfunction immediately posttransplantation can vary from subtle slowing of the expected decrease in creatinine concentration to frank oliguria requiring dialysis therapy for days to weeks. Risk factors for slow and delayed graft function include prolonged preservation, older donor age, and high plasma renin activity in the recipient. Cyclosporine (CsA) nephrotoxicity is another cause of early kidney allograft dysfunction. OBJECTIVE: To evaluate early kidney allograft function in patients who received low-dose CsA therapy for 48 hours before transplant surgery for comparison with that in recipients who received CsA therapy after improvement in allograft function. PATIENTS AND METHODS: In a case-control comparative study, 66 kidney recipients were divided into 2 groups on the basis of time of initiation of CsA therapy. In group 1, patients received CsA, 100 mg twice a day, for 48 hours before surgery, and in group 2, patients received CsA therapy after surgery when allograft function had improved (serum creatinine concentration

Biphasic insulin aspart 30 treatment improves glycaemic control in patients with type 2 diabetes in a clinical practice setting: experience from the PRESENT study.

AIM: The Physicians' Routine Evaluation of Safety and Efficacy of NovoMix 30 Therapy (PRESENT) study aims to assess the safety and efficacy of biphasic insulin aspart 30 (BIAsp 30) in patients with type 2 diabetes mellitus in routine clinical practice. METHODS: This was a 6-month, prospective, multinational, multiethnic observational study involving 21 977 patients from 13 countries (India, Iraq, Jordan, Kuwait, Lebanon, Qatar, Romania, Russia, Saudi Arabia, South Africa, South Korea, Turkey and the United Arab Emirates). The patients were transferred to BIAsp 30 with or without oral antidiabetic drugs (OADs) from prior treatment with OAD (n = 8583), insulin (n = 5942), OAD + insulin (n = 4673) or diet (i.e. treatment naive) (n = 1707). One thousand and seventy-two patients had incomplete or no information on previous treatment. RESULTS: At 3 and 6 months, significant reductions from baseline were observed in the mean haemoglobin A(1c) (HbA(1c)) (-1.33 and -1.81%), fasting plasma glucose (-3.02 and -3.74 mmol/l) and postprandial plasma glucose (-4.76 and -5.82 mmol/l) (p < 0.001). A significantly greater proportion of patients achieved target HbA(1c) of less than 7% at 3 months (15.3%) and 6 months (27.7%) compared with baseline (4.8%) (p < 0.001). Overall, the mean HbA(1c) at 6 months was lowered in patients regardless of prior treatment: -2.15% (OAD), -1.45% (insulin), -1.47% (OAD + insulin) and -2.35% (treatment naive). In the overall cohort, the rate of total hypoglycaemia was reduced from 5.4 events per patient-year at baseline to 2.2 events per patient-year at study end (p < 0.001). Among prior treatment subgroups, the rates of total hypoglycaemia were reduced from 2.5 to 2.1 events per patient-year in the OAD group, from 9.6 to 2.2 events per patient-year in the insulin group and from 7.6 to 2.5 events per patient-year in the OAD + insulin group but were increased from 1.0 to 1.8 events per patient-year in the treatment-naive group (p < 0.001). There were 444 adverse drug reactions (ADRs), including 13 serious ADRs: lipodystrophy (three events), symptoms of generalized hypersensitivity (two events), acute painful neuropathy (one event), worsening of diabetic retinopathy (one event), oedema (one event) and unspecified ADRs (five events). CONCLUSION: The use of BIAsp 30 monotherapy or in combination with OADs in clinical practice was effective and safe in patients with poorly controlled type 2 diabetes mellitus.

Biphasic insulin aspart 30 treatment in patients with type 2 diabetes poorly controlled on prior diabetes treatment: results from the PRESENT study.

AIM: The safety and efficacy of biphasic insulin aspart (BIAsp30) were evaluated in patients uncontrolled on previous treatment (human insulin +/- oral hypoglycaemic agent [OHA] or OHA only) in routine clinical practice. METHODS: This was a large, multi-national, multicentre, prospective, 6-month study in type 2 diabetes mellitus patients who were prescribed BIAsp30. Changes in glycated haemoglobin (HbA(1c)), fasting plasma glucose (FPG), postprandial plasma glucose (PPPG), proportion who achieved target HbA(1c) < 7% and rate of hypoglycaemic episodes were assessed. This paper evaluates outcomes in patients by diabetes duration (< 5, 5-10, 10-20 or >/= 20 years) stratified by prior therapy. RESULTS: After 6 months of treatment, glycaemia improved significantly across the duration subgroups. The improvement was better in insulin-naïve group versus prior insulin group: HbA(1c) decreased approximately 2.2%-points versus approximately 1.6%-points, FPG decreased approximately 4.5 mmol/L versus approximately 2.9 mmol/L and PPPG decreased approximately 6.8 mmol/L versus approximately 5.0 mmol/L. Target HbA(1c) was achieved by about one in four patients although insulin-naïve patients achieved this at comparatively lower BIAsp30 dose. Body weight remained relatively unchanged. Hypoglycaemic episodes appeared to be more frequent in the prior insulin group which decreased during the treatment period. CONCLUSIONS: According to this observational study, in clinical practice, initiating or transferring uncontrolled patients to biphasic insulin aspart improved glycaemic control without using a strict insulin algorithm.