Relationship between pregnancy outcomes and maternal vitamin D and calcium intake: A cross-sectional study

Poor maternal vitamin D status affects fetal and infant skeletal growth. The aim of the present study was to determine the association between newborn outcomes and maternal calcium and vitamin D intakes. Four hundred and forty-nine pregnant women, healthy at the point of delivery, and their newborns were enrolled in the study, which was performed in three university hospitals in Tehran in March 2004. Maternal anthropometric data and energy, protein, calcium and vitamin D intakes were collected, and newborn outcomes (weight, length, head circumference and 1-min Apgar score) were determined. Almost two-thirds of the mothers (64.3%) took no supplements during pregnancy. Only one-third of the mothers (33.8%) had adequate intakes of calcium and vitamin D (from supplements and foods) compared with the Recommended Dietary Allowances. Mean length at birth and 1-min Apgar score were higher in newborns whose mothers had adequate calcium and vitamin D intake than in newborns whose mothers had inadequate intake (p = 0.03 and p = 0.04, respectively). Significant correlations were found between adequate maternal calcium and vitamin D intake and both appropriate birth weight and 1-min Apgar score of newborns and weight gain of mothers during pregnancy. Informing mothers of the critical importance of consuming adequate amounts of calcium and vitamin D seems necessary.     

Investigating Genetic Mutations in a Large Cohort of Iranian Patients with Congenital Hyperinsulinism

Objective:Congenital hyperinsulinism (CHI) is the most frequent cause of severe and persistent hypoglycaemia from birth. Understanding the pathophysiology and genetic defects behind hyperinsulinism and its complications provides clues to timely diagnosis and management. The aim of this study was to evaluate the underlying genetic aetiology of a specific Iranian pediatric cohort with CHI.Methods:A total of 44 unrelated children, 20 girls and 24 boys, with an initial diagnosis or history of CHI from all regions of Iran were recruited between 2016 and 2019. Targeted next generation sequencing (tNGS) was performed for the genes found in about half of CHI patients.Results:Mutations were identified in 24 cases (55%). Patients with a confirmed genetic cause were mainly diagnosed below age of one year old (p=0.01), had fewer other syndromic features, excluding seizure, (p=0.03), were less diazoxide responsive (p=0.04) and were more diazoxide unresponsive leading to pancreatectomy (p=0.007) compared to those with no identified mutations. Among 24 patients with identified genetic mutations, 17 (71%) had a mutation in ABCC8, 3 (12%) in KCNJ11, 3 (12%) in HADH, and 1 patient had a mutation in KMT2D. These included five novel mutations in ABCC8, KCNJ11, and KMT2D.Conclusion:This is the biggest genetic study of CHI in Iran. A high frequency of recessive forms of CHI, especially HADH mutations, in our study could be due to a high rate of consanguineous marriage. We recommend tNGS to screen for all the CHI genes.     

Evaluation of the effect of pentoxifylline on white blood cell count in serum and peritoneal fluid in female rats with endometriosis

AIM: Endometriosis is defined as the growth of endometrium outside of the uterus in ectopic places. Immune system disturbances have an important role in endometriosis which may lead to infertility. It seems that inflammatory cytokines, specially tumor necrosis factor-alpha (TNF-alpha), which are produced by activated macrophages, play an important role in the pathology of endometriosis. Based on this theory, anti-TNF-alpha drugs are suggested as new drugs for endometriosis. This experimental study has been performed on female rats to determine the effect of pentoxifylline on the white blood cell count in serum and peritoneal fluid. METHODS: During the proestrous phase, one horn of the bicorn uterus of rats was removed surgically, and the endometrium implanted to different places as follows: subcutaneous, peritoneum and near the ovaries. After 2 months' observation, female rats were divided randomly into two groups. The treated group (n = 10) were given pentoxifylline (5 mg/kg twice a day), and the control group (n = 10) were given normal saline (the same dose), which was injected subcutaneously. Then via second laparotomy and in the same phase of the cycles, the size of implants and the white blood cell levels in the serum and peritoneum were measured. RESULTS: In the treated group, the total implant mass (mm2) decreased significantly in the right subcutaneous (8.05 mm2 vs 13.5 mm2; P = 0.01), left subcutaneous (7.64 mm2 vs 14.00 mm2; P = 0.01), right ovary (6.64 mm2 vs 15.22 mm2; P = 0.001) and left ovary (7.18 mm2 vs 14.56 mm2; P = 0.005). The total white blood cell count (5254.5455 +/- 178.73 vs 15,833.33 +/- 259.27; P = 0.02) and neutrophils (297.34 +/- 57.34 vs 2736.00 +/- 346.75; P = < 0.001) in the serum were decreased and the total count of lymphocytes (4967.92 +/- 696.194 vs 13,048.33 +/- 178.73; P = 0.003) in serum was increased. There were not any significant changes in the total white blood cell count in the peritoneum in both groups. The number of estrous cycles in both groups was similar. CONCLUSION: Based on our study, pentoxifylline could decrease the size of endometrial implants, especially in the ovaries and subcutaneous areas, and total white blood cell count in serum. Pentoxifylline could increase the lymphocyte count and decrease the neutrophil count in serum, and because these changes it might alter the immune system. Pentoxifylline did not have any adverse effect on rats' cycles and a good aspect of treatment with pentoxifylline was achieved.     

Evaluation of Validity and Efficiency of Diagnostic Criteria in Autoimmune Hepatitis in Children

Background: Autoimmune hepatitis (AIH) is a progressive inflammatory liver disease with various clinical symptoms, but treatment and prevention of hepatic failure and cirrhosis is possible with early diagnosis. However, no specific test has been approved for the diagnosis of AIH. In 2008, the International Autoimmune Hepatitis Group (IAIHG) developed a simplified diagnostic scoring system that has been widely used in practice. Nevertheless, it cannot distinguish AIH from Primary Sclerosing Cholangitis (PSC) and consensus is lacking with respect to its validity, sensitivity, and applicability for children patients. The newer 2018 version also requires validation. The present study intends to evaluate the validity and efficiency of the IAIHG simplified scoring system and new scoring system in children with AIH.Methods: The present study is a non-interventional case–control study covering 152 patients with hepatic diseases (83 patients with AIH and 69 patients with Wilson disease (WD)). Titers of autoantibodies, IgG levels, hepatic histology, and absence of viral hepatitis were scored and calculated according to IAIHG diagnostic criteria. Statistics software package (SPSS) and draft receiver operating characteristic (ROC) curves was used to analyze data and determine value of diagnostic criteria.Result: In our study, both scoring systems’ accuracy was good in AIH diagnosis, although new score displays higher sensitivity and specificity, suggestive of greater accuracy and predictive strength.Conclusion: Our study is the first validation study of the new scoring system in diagnosing AIH, and further studies require verifying this scoring system.     

Conjugation of a smart polymer to doxorubicin through a pH-responsive bond for targeted drug delivery and improving drug loading on graphene oxide

Polymeric nanoparticles have emerged as efficient carriers for anticancer drug delivery because they can improve the solubility of hydrophobic drugs and also can increase the bio-distribution of drugs throughout the bloodstream. In this work, a computational study is performed on a set of new pH-sensitive polymer–drug compounds based on an intelligent polymer called poly(β-malic acid) (PMLA). The molecular dynamics (MD) simulation is used to explore the adsorption and dynamic properties of PMLA–doxorubicin (PMLA–DOX) interaction with the graphene oxide (GOX) surface in acidic and neutral environments. The PMLA is bonded to DOX through an amide bond (PMLA-ami-DOX) and a hydrazone bond (PMLA-hz-DOX) and their adsorption behavior is compared with free DOX. Our results confirm that the polymer–drug prodrug shows unique properties. Analysis of the adsorption behavior reveals that this process is spontaneous and the most stable complex with a binding energy of −1210.262 kJ mol⁻¹ is the GOX/PMLA-hz-DOX complex at normal pH. On the other hand, this system has a great sensitivity to pH so that in an acidic environment, its interaction with GOX became weaker while such behavior is not observed for the PMLA-ami-DOX complex. The results obtained from this study provide accurate information about the interaction of the polymer–drug compounds and nanocarriers at the atomic level, which can be useful in the design of smart drug delivery systems.

Polymeric nanoparticles have emerged as efficient carriers for anticancer drug delivery because they can improve the solubility of hydrophobic drugs and also can increase the bio-distribution of drugs throughout the bloodstream.     

Nitric oxide and the liver

Abstract: In recent years, the role of nitric oxide (NO) in the pathogenesis of liver disease and its complications has been extensively studied. There remain, however, many areas of controversy. In particular, the effect of NO on vascular function in the systemic circulation and the hepatic microcirculation has received the greatest attention. It has been proposed on the one hand that increased NO synthesis is responsible for the development of the hyperdynamic circulation in cirrhosis, while decreased production of NO within the hepatic microcirculation may be important in the development of parenchymal tissue damage and the onset of portal hypertension. The purpose of this review is to examine the available data concerning the role of NO in liver disease and to discuss some of the controversies and contradictions that surround it.     

Analysis of T2 limitations and off-resonance effects on spatial resolution and artifacts in echo-planar imaging

Several aspects of blipped echo-planar imaging (EPI) are treated mathematically. An expression relating the necessary readout gradient strength and sampling time to the spatial resolution and readout duration is derived. It is shown how the net spatial resolution may be limited by the object's T2 characteristics and B0 field homogeneity, irrespective of the number of sampled points. Additionally, off-resonance effects result in a loss of spatial resolution and image distortion to a considerably greater degree than in conventional two-dimensional Fourier transform imaging. The extent of these effects is directly related to the time required to acquire the data matrix, and is therefore amplified when EPI is implemented on a standard commercial whole-body system which because of limited gradient performance uses necessarily longer sampling durations. Specific hardware modifications to a standard commercial imager are considered to allow successful EPI implementation. EPI image characteristics are compared quantitatively with those of conventional methods.     

Sympathetic Nervous System Does Not Mediate Reflex Pupillary Dilation during Desflurane Anesthesia

Background: Pupil size is determined by an interaction between the sympathetic and parasympathetic divisions of the autonomic nervous system. Noxious stimulation dilates the pupil in both unanesthetized and anesthetized humans. In the absence of anesthesia, dilation is primarily mediated by the sympathetic nervous system. In contrast, pupillary dilation in cats given barbiturate or cloralose anesthesia is mediated solely by inhibition of the midbrain parasympathetic nucleus. The mechanism by which noxious stimuli dilate pupils during anesthesia in humans remains unknown. Accordingly, the authors tested the hypothesis that the pupillary dilation in response to noxious stimulation during desflurane anesthesia is primarily a parasympathetic reflex.

Methods: In six volunteers, the alpha-1 adrenergic receptors of the iris musculature were blocked by unilateral administration of topical dapiprazole; six other volunteers were given unilateral topical tropicamide to block the muscarinic receptors in the iris. Desflurane anesthesia was subsequently induced in all volunteers. Sympathetic nervous system activation, with reflex dilation of the pupil, was produced by noxious electrical stimulation during 4% and 8% end-tidal desflurane, and by a rapid 4%-to-8% step-up in the desflurane concentration. Pupil diameter and the change in pupil size induced by a light stimulus (light reflex amplitude) were measured with infrared pupillometry.

Results: Dapiprazole drops produced a Horner's miosis, but pupils were equally small after induction of anesthesia. Pupillary dilation after noxious stimulation and desflurane step-up was identical in the unblocked and dapiprazole-blocked pupils. After tropicamide administration, the pupil was dilated and the light reflex was completely inhibited. Noxious stimulation nonetheless produced a slight additional dilation.