Multicomponent synthesis of fully substituted thiazoles using glycine-based dithiocarbamates, acetic anhydride and nitroalkenes.

Reaction of glycine-based dithiocarbamates with nitroalkenes in the presence of acetic anhydride was utilized for the synthesis of fully substituted 2-(alkylsulfanyl)-4-(nitroalkyl)-5-acyloxy-1,3-thiazoles. The reaction proceeds via the in situ formation of thiazol-5(4H)-one from glycine-based dithiocarbamates, followed by the Michael addition of this intermediate to nitroalkenes, aromatization, and esterification reaction cascade. This new one-pot three-component reaction afforded a diverse library of fully substituted thiazoles in high to excellent yields under solvent-free conditions.

Ensembling three multicomponent reactions for the synthesis of a novel category of pseudo-peptides containing dithiocarbamate and N,X-heterocylic groups.

Consecutive multicomponent reactions have been applied for the synthesis of novel pseudo-peptides bearing dithiocarbamate and N,X-heterocyclic groups (X = S, O) in only one structure. The first multicomponent reaction includes the synthesis of dithiocarbamates using an amine or amino acid, CS2 and an electrophile. The second MCR is synthesis of Asinger imines using 2-chloroisobutyraldehyde, NaXH (X = S, O), ketone and ammonia. The final MCR is Ugi reaction to afford the corresponding three-dimensional pseudo-peptides. Various Asinger imines, carboxylic acids and isocyanides were applied in this protocol to provide diversities of pseudo-peptides in high to excellent yields.

Synthesis of a novel category of pseudo-peptides using an Ugi three-component reaction of levulinic acid as bifunctional substrate, amines, and amino acid-based isocyanides.

The synthesis of a novel category of pseudo-peptides via intramolecular Ugi reaction of levulinic acid (4-oxopentanoic acid), aromatic and aliphatic amines, and amino acid-based isocyanides is reported. Levulinic acid was applied as a bifunctional substrate containing both carbonyl and acid moieties suitable for the Ugi reaction. This article provides a facile and convenient one-pot procedure for the synthesis of peptide-like heterocyclic molecules containing 2-pyrrolidone (γ-lactam), amide and ester functional groups with good to excellent yields.

In Vitro Gluten Challenge Test for Celiac Disease Diagnosis.

OBJECTIVES: The in vitro gluten challenge test is an important diagnostic modality in celiac disease (CD), especially in patients who begin treatment with a gluten-free diet before adequate diagnostic workup or in cases with atypical CD. Available literature was reviewed regarding the accuracy of the in vitro gluten challenge test for CD diagnosis. METHODS: MEDLINE, Scopus, and Google Scholar were searched, and studies that used serology and bowel biopsy as the criterion standard for diagnosis were included in our study. Data on authors, publication year, characteristics of the patient and control groups, patients' diet, duration of the gluten challenge test, histology findings, endomysial antibody (EMA) and anti-tissue transglutaminase (tTG) levels, CD markers, and intercellular cell adhesion molecule-1, and human leukocyte antigens before and after the gluten challenge test were extracted. RESULTS: Overall, 15 studies were included in this meta-analysis. Pooled sensitivity %/specificity % was 84/99 for EMA after the challenge, 52/96 for EMA without the challenge, 95.5/98.3 for anti-tTG after the challenge, and 95.1/98.3 for anti-tTG without the challenge test. Sensitivity/specificity for immunological markers were 89/97 for the percentage of CD25⁺-lamina propria lymphocytes, 96/91 for the percentage of CD3⁺-lamina propria lymphocytes, and 96.1/85.7 for the percentage of intercellular cell adhesion molecule-1-lamina propria lymphocytes. The factors that increased the sensitivity of EMA were longer test duration, and the evaluation of patients on a gluten-containing diet or short-term gluten-free diet. CONCLUSIONS: The in vitro gluten challenge test can be a useful part of the diagnostic workup of CD, rather than only a model to evaluate its mechanisms.

Moyamoya disease mimicking encephalitis.

Moyamoya disease is a rare vaso-occlusive illness with an unknown etiology characterized by stenosis of the internal carotid arteries with spontaneous development of a collateral vascular network. A 15-month-old girl was referred to the emergency ward of Imam Reza Hospital due to decreased level of consciousness, focal seizures and fever during the previous 24 hours with an impression of encephalitis. Physical examination revealed left side hemiparesis; however brain CT-Scan did not show any significant lesions. Initial therapy with vancomycin, ceftriaxone and acyclovir was administered. CSF analysis did not show any abnormality and the blood as well as CSF cultures results were negative. Brain MRI showed hyperintensity at right frontal and parietal regions, suggesting vascular lesion. Magnetic resonance angiography (MRA) showed bilaterally multiple torsions in vessels at the basal ganglia consistent with moyamoya vessels. In all children exhibiting encephalitis, vascular events such as moyamoya disease should be considered. Brain MRI is a critical tool for this purpose. Common causes of encephalitis such as herpes simplex should also be ruled out.

Diagnostic accuracy of anti-DGP (IgG) for celiac disease.

Background: Celiac disease (CD) is an autoimmune enteropathy that is caused by the intake of gluten-containing grains in genetically susceptible humans. The gliadin and glutenin parts of wheat gluten are the essential factors that cause intestinal damage. Objectives: We analyzed the performance of a time-resolved immunofluorometric assay (TR-IFMA) in the diagnosis of CD in children. For this purpose, we compared the performance of IgA anti-tissue transglutaminase antibodies (IgA anti-TTG) and IgG antibodies against deamidated gliadin peptides (IgG anti-DGP) for the diagnosis of CD. Materials and Methods: In this cross-sectional study conducted in 2021 for a duration of about 6 months, 200 patients with suspected CD symptoms, children who needed screening due to Down syndrome or Turner syndrome, and the first-degree relatives of CD patients who underwent diagnostic evaluation were enrolled in a census study. Results: This study compares existing point-of-care anti-DGP Ab (IgG) and anti-TTG Ab (IgA) tests against each other using the gold standard of duodenal biopsy and pathology. Serology as a screening test was acceptable (93.6% for anti-DGP vs. 94.2% for anti-TTG) for both of them. This equivalent sensitivity of serum TTG and the DGP tests validates its potential as a basic tool for serological testing. Furthermore, endoscopy is carried out in patients positive for both. Conclusions: Our study showed that for the diagnosis of CD, anti-DGP antibodies had comparable characteristics with anti-TTG (IgA) in terms of diagnostic specificity and sensitivity. Specify of anti-DGP was higher than that of anti-TTG.

A Comparison Between Serum Selenium Level in Febrile Children with or Without Seizure.

The role of trace elements in febrile seizure (FS) was considered recently. The present study was performed evaluating the serum level of selenium in febrile children aged 6-60 months with and without seizure. A cross-sectional study was performed in Mashhad University of Medical Sciences, Mashhad, Iran. Sixty patients aged 6-60 months including 30 children with FS and 30 febrile children without seizure were included. Blood sample was taken, and the serum level of selenium was measured. Data was analyzed using SPSS software. Sixteen patients in FS group (53.3%) and 10 patients in febrile group (33.3%) were males with an average age of 25.21 ± 15.91 and 26.47 ± 17.61 months, respectively. There was no significant difference between groups in age and sex (p = 0.77 and p = 0.19, respectively). The serum level of selenium was 87.34 ± 8.23 and 89.63 ± 9.83 µg/L in FS and febrile groups, respectively. Difference was not significant (p = 0.33). In children aged less than 1 year, the serum level of selenium in FS and febrile group was 83.32 ± 6.2 µg/L and 82.55 ± 8.32 µg/L, respectively. Difference was not significant (p = 0.87). In children aged more than 1 year, the serum level of selenium in FS significantly was lower compared to febrile group (87.96 ± 8.42 µg/L and 93.17 ± 8.66 µg/L, respectively, p = 0.04). The serum level of selenium was lower in children aged more than 1 year with febrile seizure compared to febrile ones.

Risk factors associated with life-threatening infections in children with febrile neutropenia: a data mining approach.

PURPOSE: To determine risk factors (RFs) and their relationship with life-threatening infection (LTI) in children with febrile neutropenia (FN). METHOD: In this cross-sectional study, from December 2008 to November 2009, all children with FN admitted to Dr Sheikh Pediatric Hospital were enrolled. For each patient, demographic, clinical, and laboratory data were recorded and they were followed up for occurrence of LTI. RESULTS: One hundred and twenty episodes of FN in 68 patients were analyzed. The most common underlying disease was acute lymphoblastic leukemia (53.3%), 9 (7.5%) died from an infection and 35 patients (29.1%) had a LTI. Five variables were identified as RFs for LTI, that is, body temperature ≥39°C (P=0.000), presence of mucositis (P=0.000), abnormal chest x-ray (P=0.001), platelet count <20,000/mm (P=0.000), and absolute neutrophil count <100/mm (P=0.001). Risk of LTI was increasing according to number of RFs presented at the beginning of admission (from 2.8% in patients without RF to 100% in patients with 5 RF). Data mining analysis showed relationship between RFs with platelet count as the most important variable in the high-risk group for LTI. CONCLUSIONS: Evaluation of important RFs and judging the severity of patients' condition by studying the importance and relationship between RF at the time of admission can be a useful method for screening LTI in children with FN.

Etiology of gastrointestinal bleeding in children referred to pediatric wards of Mashhad hospitals, Iran.

BACKGROUND: Gastrointestinal (GI) bleeding, which has several clinical manifestation and origins, is known as one of the most life-threatening events in children. Several etiologies have been suggested for GI bleeding. OBJECTIVE: To determine the most important causes of GI bleeding in children referred to Ghaem Hospital and Dr. Sheikh Hospital, Mashhad, Iran. METHODS: In this cross-sectional study, after obtaining written informed consent of their parents, 113 patients aging from newborn infants to 18-year-old children with GI bleeding admitted to Ghaem Hospital and Dr. Sheikh hospital were enrolled in this study from June 2012 to June 2014. After performing routine diagnostic and therapeutic procedures, a checklist containing all necessary information including demographic data, clinical history of patients, endoscopy and pathology findings, clinical and preclinical information were collected. The data were then analyzed using Statistical Package for the Social Sciences (SPSS) version 16. RESULTS: Of a total 113 study children, 61 (54%) were male and 52 (46%) were female. The results of this study showed that the most important causes of bleeding in upper GI among all admitted patients were prolapse gastropathy (18.6%), esophagitis (15.9%) and esophageal varices, gastritis, and coagulopathy (7.1% for each). The main causes of lower GI bleeding were polyp (32.5%), chronic nonspecific colitis (20.7%), and proctitis (18.2%). CONCLUSION: Findings of this study indicated that prolapse gastropathy and esophagitis are more prevalent causes of upper GI bleeding. Furthermore, esophageal varices were more common in children older than 13 years. Polyp, chronic nonspecific colitis and proctitis are the most prevalent causes of lower GI bleeding.

A multi-strain Synbiotic may reduce viral respiratory infections in asthmatic children: a randomized controlled trial.

BACKGROUND AND OBJECTIVE: Asthma is a growing problem worldwide. Acute exacerbations impose considerable morbidity, mortality, and increased cost. Viral respiratory infections are the most common cause (80-85%) of pediatric asthma exacerbations and admissions to the hospital. The aim of this study was to determine the effect of a new synbiotic Lactocare® on viral respiratory infections and asthma exacerbations in asthmatic children. METHODS: In this double blind, placebo-controlled, randomized clinical trial, 72 children with mild persistent asthma, aged between 6 and 12 years, were randomized to receive either Lactocare®, a Synbiotic containing 1 billion CFU/Capsule of Lactobacillus casei, Lactobacillus rhamnosus, Streptococcus thermophilus, Bifidobacterium breve, Lactobacillus acidophilus, Bifidobacterium infantis, Lactobacillus bulgaricus, and Fructooligosacharide (Zist Takhmir, Tehran, Iran) or placebo daily for 60 days. The primary outcome was the number of viral respiratory infections, and secondary outcomes were school absence, salbutamol and prednisolone usage, outpatient visits, and hospital admission for asthma. The outcomes were compared among study groups using the SPSS 11.5 program and the Mann Whitney and Fisher exact tests. RESULTS: Of the 72 children who were enrolled with mild persistent asthma, 36 were assigned randomly to be treated with synbiotic and 36 with placebo. The number of viral respiratory infections was significantly higher in placebo group than the synbiotic group during the first month of intervention (0.74 ± 0.12 vs. 0.44 ± 0.1, p < 0.007) but not during the second month (0.5 ± 0.8 vs. 0.5 ± 0.8, p < 0.641). Considering the total duration of the study (two months), infection episodes also were significantly lower in the synbiotic group (0.92 ± 0.15 vs. 0.69 ± 0.11, p < 0.046). Salbutamol consumption was significantly lower in the synbiotic group, but there were no significant differences in school absenteeism, oral prednisolone use, outpatient visits, or hospital admissions. CONCLUSION: This new synbiotic (a mixture of seven probiotic strains plus fructooligosacharide may reduce episodes of viral infection in asthmatic children. TRIAL REGISTRATION: This study is registered in Iranian Registry of Clinical Trials with registration number of IRCT201509234976N3. FUNDING: This research was supported financially by the Research Council of Mashhad University of Medical Sciences (Grant Number: 911048).

Probiotic for irritable bowel syndrome in pediatric patients: a randomized controlled clinical trial.

BACKGROUND: Irritable bowel syndrome (IBS) is a common gastrointestinal disorder in children. Recently, probiotics have been suggested as a treatment option for gastrointestinal disorders. The most effective species and the most appropriate doses are still unknown. OBJECTIVE: The aim of this study was to assess the effects of Lactobacillus GG (LGG) for treating IBS in pediatric patients. METHODS: In a controlled, double blind, randomized trial, patients with IBS diagnosed by Rome III criteria from August 2012 to September 2012 at Dr. Sheikh Hospital, Mashhad University of Medical Sciences, Iran, were assigned to one of two groups, i.e., intervention and control groups. For four weeks, the intervention group received a probiotic in capsule form that contained LGG at a concentration of 1×10(10) cfu/ml bacteria. For the same period, the control group received a placebo capsule that had the same shape and color but only contained inulin, which also was present in the LGG capsules. The primary outcome was any change in the severity of the patients' pain, and we used a five-point Likert scale to evaluate the severity of their pain. Secondary outcomes were ghanges of the functional scale, stool patterns, and associated problems. RESULTS: Fifty-two patients participated in the study, and 26 patients were assigned randomly to each of the two groups. The severity of the patients' pain decreased significantly in the intervention group after one, two, three, and four weeks of treatment, as indicated by P-values of 0.01, 0.00, 0.00, and 0.00, respectively. Also, there was significant improvement in the functional scale after two weeks of treatment (P-value ≤ 0.00). CONCLUSION: Lactobacillus GG at a concentration of 1×10(10) cfu/ml for a period of four weeks can lessen the severity of the patients' pain and improve the functional scale in patients with irritable bowel syndrome. Probiotics can have therapeutic effects for IBS patients.

Ingested Foreign Bodies Removed by flexible Endoscopy in Pediatric Patients: A 10-year Retrospective Study [corrected].

INTRODUCTION: Determination of type and location of trapped objects and endoscopic observations among children with foreign-body ingestion. MATERIALS AND METHODS: We evaluated 105 endoscopic records of patients presenting with foreign-body ingestion from 2001-2011. RESULTS: Button batteries were the most common objects removed (41%). The lower segment of the esophagus was the most common trapping site. There was significant correlation between type of foreign body and its location of trapping. Abnormal endoscopic observations were reported in 33% patients. There was significant correlation between the type of foreign body and endoscopic observations. There was also a significant correlation between the location of the foreign body and endoscopic observation. CONCLUSION: The pattern of foreign-body ingestion is somewhat different in our center compared with other studies. Awareness among parents about the prevention of this accident is an important step in decreasing the incidence of foreign-body ingestion.

Diagnostic accuracy of nuclear medicine imaging in protein losing enteropathy : systematic review and meta-analysis of the literature.

BACKGROUND AND AIM: Scintigraphy using Tc-99m or In-111 labeled proteins is an important diagnostic modality for diagnosis of protein losing enteropathy (PLE). We systematically reviewed the available literature regarding the accuracy of scintigraphy using Tc-99m or In-111 labeled proteins for diagnosis of PLE. METHODS: Medline and SCOPUS were searched using (("protein losing") AND ("scintigraphy" OR "Nuclear Medicine")) as keywords without any language or date limit. All studies on the accuracy of scintigraphy using Tc-99m or In-111 labeled proteins in PLE were included in the systematic review. RESULTS: Overall 12 studies were included in our study. Pooled sensitivity and specificity were 87% [81-92%], and 62% [51-72%], respectively. Tc-99m labeled tracers had higher sensitivity but lower specificity compared to In-111 labeled ones. Delayed imaging could increase the sensitivity of imaging despite the lower specificity compared to the early images. Restriction of the analyses to larger studies (more than 10 patients) and to studies with the gold standard of fecal alphal-antitrypsin did not change the pooled indices. CONCLUSION: Scintigraphy using Tc-99m or In-111 labeled proteins has high sensitivity for diagnosis and localization of PLE. Using Tc-99m labeled tracers and delayed imaging can further increase the sensitivity. Despite the high sensitivity, specificity of scintigraphy is suboptimal and false positive abdominal activities can limit the usefulness of this imaging method.

Pentoxifylline in hepatopulmonary syndrome.

AIM: To determine the effects of pentoxifylline (PTX) on clinical manifestations and evaluate arterial blood gas data in hepatopulmonary syndrome (HPS) in children. METHODS: In a pilot study of 10 children with chronic liver disease, who had HPS, 20 mg/kg/d PTX was administered for 3 mo. Clinical data and arterial blood gas parameters were evaluated at baseline, the end of the treatment period, and 3 mo after drug discontinuation. RESULTS: Six patients could tolerate PTX, while four patients experienced complications. Among patients who could tolerate PTX, there was a significant increase in arterial oxygen pressure (PaO(2)) (P = 0.02) and oxygen saturation (SaO(2)) (P = 0.04) and alveolar-arterial oxygen gradient (P = 0.02) after 3 mo of treatment. Significant decreases in PaO(2) (P = 0.02) and alveolar-arterial oxygen gradient (P = 0.02) were also seen after drug discontinuation. CONCLUSION: PTX may improve PaO(2), SaO(2) and alveolar-arterial oxygen gradient in the early stage of HPS.

Autoimmune Lymphoproliferative Syndrome (ALPS) in a Boy with Massive Lymphadenopathy.

Autoimmune lymphoproliferative syndrome (ALPS) is an uncommon nonmalignant lymphoproliferative disease which is characterized by chronic, persistent or recurrent lymphadenopathy, splenomegaly, hepatomegaly, immune cytopenia , hypergammaglobinemia and increased risk of lymphoma. We report a 2-year old boy with hepatosplenomegaly as first presentation. Petechial and purpuric rashes with massive cervical lymphadenopathies developed 10 months later.In laboratory tests anemia, thrombocytopenia and hypergammaglobinemia were observed. According to flocytometry increased double negative T cells and by apoptosis assay decrease apoptosis of lymphocytes accompanied clinical manifestations, thus diagnosis of ALPS was established. In conclusion; in all patients with massive lymphadenopathy and hepatosplenomegay; especially with cytopenia; ALPS should be considered.