Meta-analysis of epigenome-wide association studies of carotid intima-media thickness

Common carotid intima-media thickness (cIMT) is an index of subclinical atherosclerosis that is associated with ischemic stroke and coronary artery disease (CAD). We undertook a cross-sectional epigenome-wide association study (EWAS) of measures of cIMT in 6400 individuals. Mendelian randomization analysis was applied to investigate the potential causal role of DNA methylation in the link between atherosclerotic cardiovascular risk factors and cIMT or clinical cardiovascular disease. The CpG site cg05575921 was associated with cIMT (beta?=??0.0264, p value?=?3.5?×?10^–8) in the discovery panel and was replicated in replication panel (beta?=??0.07, p value?=?0.005). This CpG is located at chr5:81649347 in the intron 3 of the aryl hydrocarbon receptor repressor gene (AHRR). Our results indicate that DNA methylation at cg05575921 might be in the pathway between smoking, cIMT and stroke. Moreover, in a region-based analysis, 34 differentially methylated regions (DMRs) were identified of which a DMR upstream of ALOX12 showed the strongest association with cIMT (p value?=?1.4?×?10^–13). In conclusion, our study suggests that DNA methylation may play a role in the link between cardiovascular risk factors, cIMT and clinical cardiovascular disease.

     

Glomerulopathy in patients with dermatomyositis in early active disease: clinical,pathological and capillaroscopic manifestations,and response to treatment

IntroductionIdiopathic inflammatory myopathies (IIMs) are a group of systemic connective tissue diseases that present with muscular and extra-muscular manifestations. There are few reports on kidney involvement, especially in dermatomyositis (DM) patients. We evaluated the clinical, laboratory, capillaroscopy, and kidney pathology of patients with DM, who presented with proteinuria during the first year, and followed them for response to treatment.Material and methodsWe evaluated 205 patients with proximal muscle weakness or high muscle enzymes, who referred to the nailfold capillaroscopy clinic from April 2010 to October 2021. Seventy-four patients fulfilled the New 2017 EULAR/ACR Classification Criteria for adult and juvenile IM with probability of ≥ 90% for DM with duration of ≤ 12 months and proteinuria > 350 mg/24 hours. All manifestations of patients with glomerulopathy and their kidney biopsies were reviewed, and they were followed for their treatment response.ResultsFrom 74 patients with DM, 52 female and 22 male, median age 37 (19–65) years, and disease duration of median 4.5 (1–12) months, 2 (2.7%) patients (25- and 28-year-old male) had proteinuria. Their kidney biopsy showed mesangioproliferative glomerulonephritis (GN). There was no case of acute or chronic kidney damage or rhabdomyolysis. Both had high disease activity, high erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), abnormal capillaroscopy, and high anti-Ro positivity with good early response of their kidney function, muscle weakness, and laboratory tests after immunosuppressive treatment for 3–6 months. One patient had capillaroscopy follow-up, and all abnormalities were resolved in 8 fingers. One patient, due to poor follow-up, after 8 months had recurrence of his disease.ConclusionsWe found mesangioproliferative GN as a rare extra-muscular manifestation in patients with DM in the active and early phase of the disease. Full immunosuppressive treatment showed early complete recovery in these patients.     

A placebo-controlled study of tropisetron added to risperidone for the treatment of negative symptoms in chronic and stable schizophrenia

Rational

A growing body of evidence illustrates that 5-HT3 receptor antagonist drugs may be of benefit in the treatment of negative symptoms in schizophrenia.

Objective

The objective of this study was to assess the efficacy and tolerability of tropisetron add-on to risperidone on negative symptoms in patients with chronic stable schizophrenia.

Methods

In a double-blind, placebo-controlled 8-week trial, 40 patients with chronic schizophrenia who were stabilized on risperidone were randomized into tropisetron or placebo add-on groups. Psychotic symptoms were measured using the Positive and Negative Syndrome Scale (PANSS) every 2 weeks. Furthermore, extrapyramidal and depressive symptoms as well as side effects were assessed. The primary outcome measure was the difference in change from baseline of negative subscale scores between the two groups at week 8.

Results

Tropisetron resulted in greater improvement of the total PANSS scores [F(1.860,70.699)?=?37.366, p?<?0.001] as well as negative scores [F(2.439,92.675)?=?16.623, p?<?0.001] and general psychopathology [F(1.767,67.158)?=?4.602, p?=?0.017], but not positive subscale scores [F(1.348, 51.218)?=?0.048, p?=?0.893] compared to placebo. In a multiple regression analysis controlling for positive, extrapyramidal, and depressive symptoms, treatment group (standardized β?=??0.640) significantly predicted changes in primary negative symptoms. The side effect profile did not differ significantly between the two groups.

Conclusion

Tropisetron add-on to risperidone improves the primary negative symptoms of patients with chronic stable schizophrenia.     

Ionized and total magnesium concentration in patients with severe preeclampsia-eclampsia undergoing magnesium sulfate therapy

AIM: As ionized magnesium is the active form of magnesium and exerts a therapeutic effect, the present study was performed to determine the levels and correlations between ionized and total magnesium under baseline and therapeutic conditions in patients with severe preeclampsia and eclampsia receiving magnesium sulfate. METHODS: Fifty singleton patients with severe preeclampsia received a loading dose of 4 g of magnesium sulfate, followed by 2 g per hour as maintenance dose until 24 h after delivery, or 24 h after the last seizure in case of postpartum convulsions. Serial blood samples were taken before magnesium sulfate infusion, 30 min and 240 min after the initiation of the infusion and 4 h after the discontinuation of the drug. Data were analyzed by repeated measure ANOVA and paired t-test. RESULTS: Baseline levels of total and ionized magnesium were 2.4+/-0.6 mEq/L and 1.3+/-0.5 mEq/L (mean+/-SD), respectively. Putative level of 4 mEq/L of total magnesium was not obtained in up to 42% of patients during the treatment. There was not any significant correlation between the two forms of magnesium under baseline and therapeutic conditions. CONCLUSION: Despite the effectiveness of the standard regimen of magnesium sulfate in the treatment and prevention of eclamptic seizures, it can not provide the proposed therapeutic level of magnesium in all patients. With respect to the lack of correlation between ionized and total magnesium, further studies are necessary to investigate the superiority of measurement of ionized, rather than total magnesium, for titration of therapeutic magnesium sulfate infusion.     

Factors Associated with Tobacco Use among Iranian Adolescents: An Application of Protection Motivation Theory

Background: Tobacco use is a significant predisposing factor to many diseases. Protection motivation theory is a well-suited theory, since fear can motivate individuals to change their unhealthy behaviors. Objective: This study was conducted to examine the associations between the constructs of this theory with intention and tobacco use behavior. Method: The present cross-sectional study was conducted in Noshahr, Iran. The participants were 440 high school boys selected using a stratified random sampling in 2016. A questionnaire about tobacco use based on protection motivation theory was developed and its validity and reliability were assessed. The questionnaire included the demographic information, the constructs of theory, and tobacco use behavior. Structural equation modeling was used to test the associations between the constructs with intention and tobacco use. Results: The variables of perceived vulnerability (β = 0/137, P < 0.001), fear (β = 0/149, P < 0.001), self-efficacy (β = 0/249, P < 0.001), perceived intrinsic reward (β = ?0.285, P < 0.001), threat appraisal (β = ?0.25, P < 0.001), and coping appraisal (β = 0.358, P < 0.001) had direct effect and are significant with intention. Moreover, perceived vulnerability (β = ?0.158, P < 0.001), fear (β = ?0.172, P < 0.001), self-efficacy (β = ?0.288, P < 0.001), perceived intrinsic reward (β = 0.329, P < 0.001), threat appraisal (β = 0.265, P < 0.001), and coping appraisal (β = ?0.379, P < 0.001) affected tobacco use indirectly through intention and were significantly associated with behavior. Also, intention had direct effect and is significant with tobacco use (β = ?1.156, P < 0.001). Conclusions: The protection motivation theory provides a useful framework for investigating factors of tobacco use among male students. Future tobacco prevention interventions should focus on increasing the vulnerability and fear, decreasing intrinsic reward, and improving self-efficacy to reduce tobacco use.     

SB‐334867, an orexin receptor 1 antagonist,decreased seizure and anxiety in pentylenetetrazol‐kindled rats

Convulsive seizures are due to abnormal synchronous and repetitive neuronal discharges in the central nervous system (CNS). Finding new therapeutics to overcome the side effects of the current drug therapies and to increase their effectiveness is ongoing. Orexin‐A and orexin‐B are brain neuropeptides originating from postero‐lateral hypothalamic neurons. Studies show that orexins, through activation of OX1 and OX2 receptors, have excitatory effects in the CNS. Accordingly, this study was designed to evaluate the effect of OX1 receptor antagonist (SB‐334867) on seizure‐ and anxiety‐related behaviors of pentylenetetrazol (PTZ)‐kindled rats. Kindling was induced by repeated intraperitoneal (IP) injections of PTZ (32 mg/kg) with two‐day intervals for 24 days in male Wistar rats. Three groups received intracerebroventricular (ICV) injections of SB‐334867 (2.5, 5, and 10 μg/rat) before PTZ injections. Two control groups received vehicle (2 μL/rat, ICV) and valproate (26 μg/rat, ICV) before PTZ injections. An extra group of control animals received saline both ICV and IP. Seizure‐related behaviors were monitored for 30 min following PTZ administration. The anxiety‐like behaviors were also assessed using elevated plus‐maze in the first and last days of the study. The results revealed that ICV injection of SB‐334867, mainly at the dose of 10 μg/rat, decreased the median of seizure stages, prolonged the latency and reduced the duration of different seizure stages, and reversed the PTZ‐induced anxiety‐like behaviors. Based on the presented results, it is suggested that pharmacological blockade of the OX1 receptor is a potential target in the treatment of seizure and concomitant anxiety disorders.     

Aflatoxin B1 effects on ovarian follicular growth and atresia in the rat

For this investigation, 28 female healthy adult Wistar rats were selected. The animals were divided into four groups (n?=?7 per group): control, test group 1, test group 2 and test group 3. Each rat in test groups 1, 2 and 3, received 0.8 ppm, 1.6 ppm and 3.2 ppm aflatoxin B1 (AFB1), respectively, via gavage for a period of 25 days. The control group received distilled water only. All tissue specimens were processed for routine paraffin embedding and serial cross-sections cut at 5–7 μm and stained with haematoxylin–eosin. Both histomorphologic and histomorphometric analysis was performed under light microscopy. An increase in the concentration of AFB1 resulted in a reduction in the population of healthy primordial, primary, secondary and tertiary follicles. The greatest reduction was in seen in group 3 (with 3.2 ppm AFB1/day). In all test groups, due to an increase in AFB1 concentration, in both the right and left ovaries, all types of atretic follicles, including primordial, primary, secondary, and tertiary atretic follicles were significantly increased (P?<?0.01). In conclusion, AFB1 is toxic for all type of ovarian follicles, including non-growing and growing follicles and exerts an atretogenic effect on all types of ovarian follicles. The atretogenic effect of AFB1 is dose dependant. Due to its toxic effects (gametotoxicity), the resting pool of ovarian follicles (primordial follicles) decreases significantly. The ovulatory follicular population either decreases or is completely depleted.     

Ethnobotanical Study of Medicinal Plants Used by Kurd Tribe in Dehloran and Abdanan Districts,Ilam Province,Iran

This paper provides significant ethnobotanical information on pharmaceutical plant uses, where some degree of acculturation exists, so that there is urgency in recording such data. The aim of this work is to catalogue, document, and make known the uses of plants for folk medicine in Dehloran and Abdanan districts, Ilam Province, Iran. An analysis was made of the species used, parts of the plant employed, preparation methods, administration means, and the ailments treated in relation to pathological groups. A folk botanical survey was carried out from February 2007 to October 2009. The information was collected from 81 persons (60% men and 40% women) in 20 villages. The informants reported data on 122 species, belonging to 49 botanical families, were claimed as medicinal. This work is focused on human medicinal plant uses, which represent 95% of the pharmaceutical uses. The most commonly represented families were Asteraceae (37.5%), Lamiaceae (20.8%), Rosaceae (18.7%), Fabaceae (16.7%) and Apiaceae (14.6%). Some of the uses were found to be new when compared with published literature on ethnomedicine of Iran. The folk knowledge about medicinal plant use is still alive in the studied region, and a number of scarcely reported plant uses has been detected, some of them with promising phytotherapeutical applications. The results of the study reveal that some of species play an important role in primary healthcare system of these tribal communities.     

Proposed model for in vitro interaction between fenitrothion and DNA,by using competitive fluorescence, 31P NMR, 1H NMR,FT-IR,CD and molecular modeling

In this work we proposed a model for in vitro interaction of fenitrothion (FEN) with calf thymus-DNA by combination of multispectroscopic and two dimensional molecular modeling (ONIOM) methods. The circular dichroism results showed that FEN changes the conformation of B-DNA and caused some changes to C-DNA form. The FT-IR results confirmed a partial intercalation between FEN and edges of all base pairs. The competitive fluorescence, using methylene blue as fluorescence probe, in the presence of increasing amounts of FEN, revealed that FEN is able to release the non-intercalated methylene blue from the DNA. The weak chemical shift and peak broadening of ¹H NMR spectrum of FEN in the presence of DNA confirmed a non-intercalation mode. The ³¹P NMR showed that FEN interacts more with DNA via its –NO₂ moiety. The ONIOM, based on the hybridization of QM/MM (DFT, 6.31++G (d,p)/UFF) methodology, was also performed by Gaussian 2003 package. The results revealed that the interaction is base sequence dependent, and FEN interacts more with AT base sequences.