A challenging case of COVID-19: a COVID-19 positive adolescent presented with severe diabetic ketoacidosis, resistant hypertension.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a virus which causes COVID-19. It binds to the angiotensin-converting enzyme 2 (ACE2) receptors, expressed in key metabolic organs and tissues, including pancreatic beta cells, adipose tissue, the small intestine, and kidneys. This condition has been linked to a variety of additional symptoms, including acute encephalopathy, changes in consciousness, and even gastrointestinal bleeding. CASE PRESENTATION: In this study, we have reported a 13-year-old boy, 69 kg, with SARS-COV-2 infection. In this case, multiple systems, including the endocrine, renal, pulmonary, gastrointestinal, and nervous systems, were affected. CONCLUSIONS: It is speculated that different manifestations of COVID-19 can be seen in clinical settings, and practitioners should be more cautious not to miss the chimeric characteristics of COVID-19 infection.

Application of radiolabeled peptides in tumor imaging and therapy.

Scientists are looking for new therapies to cope with the rise in cancer worldwide. Since cancer cells overexpress peptide receptors and owing to small size, easy uptake by tumor cells, easy preparation, and with no toxicity, the use of radiolabeled peptides with high specificity and affinity for accurate imaging and therapy has attracted much attention. To develop an ideal imaging or treatment radiolabeled peptide, there are some aspects in the components of radiolabeled peptide including radionuclide, peptide, chelator, and spacer that should be considered. Some peptides, including somatostatin, RGD, neurotensin, bombesin, exendin, vasoactive intestinal peptide, and gastrin are currently under (pre)clinical investigations. Today, nanoparticles are suitable tools for targeting peptide for molecular imaging and therapy of tumors with low toxicity. This paper presents some essential aspects in developing a valuable radiolabeled peptide and some radiolabeled peptides with regard to their applications in tumor imaging and therapy in pre-clinical and clinical phases.

Biochemical parameters of rickets in Iranian children: A systematic review and meta-analysis.

BACKGROUND: Many causes can lead to childhood rickets. We aimed to investigate the biochemical symptoms of childhood rickets with systematic review and meta-analysis. MATERIALS AND METHODS: Seven articles published from 1975 to 2018 were recruited. The literature search was performed in the Scientific Information Database, Google Scholar, PubMed, and Elsevier databases using related keywords. For meta-analysis, the results of the studies were pooled using the random-effects model. The heterogeneity between the studies was checked using Q test and I 2 index. RESULTS: The total sample population consisted of 933 children with biochemical symptoms of rickets (133 participants per article). According to our findings, the mean serum levels of PO4, Ca, and alkaline phosphatase in children with rickets were 4.18 (95% confidence interval [CI]: 3.75-4.61, I 2 = 98.3%, P < 0.001), 9.23 (95% CI: 8.78-9.68, I 2 = 99.6%, P < 0.001), and 1.33 (95% CI: 1.23-1.44, I 2 = 95.6%, P < 0.001), respectively. CONCLUSION: Characterizing the biochemical symptoms of rickets in children can help to early diagnose and prevent the disease in children. Furthermore, educating parents about biochemical symptoms can lead to early diagnosis and successful treatment of rickets in children.

A Case of Tyrosinemia Type III with Status Epilepticus and Mental Retardation.

Tyrosinemia type III is an autosomal recessive disorder caused by the deficiency of 4- hydroxyphenylpyruvate dioxygenase (4-HPPD). It is characterized by elevated levels of blood tyrosine and massive excretion of its derivatives into the urine. Clinical findings of tyrosinemia type III include neurological symptoms and mental retardation. Only a few patients presenting with this disease have been described, and the clinical phenotype remains variable and unclear. We present a case, who was admitted to the hospital at the age of 4 months for recurrent seizures. Two months later, she was admitted again with status epilepticus. Laboratory data showed increased level of tyrosine in the blood. She was treated with a diet low in tyrosine and phenylalanine and anamix formula that leading to catch-up growth and improvement of her symptoms. Plasma tyrosine level dropped to normal values. In any child who presents with the neurologic symptom, some rare diagnosis like tyrosinemia type III should be considered.

Is there any association between urinary metabolites of polycyclic aromatic hydrocarbons and thyroid hormone levels in children and adolescents?

Considering the possible effects of polycyclic aromatic hydrocarbons (PAHs) on thyroid function, the current study aims to investigate the association of PAH urinary metabolites with the level of thyroid hormones in a sample of Iranian children and adolescents. This cross-sectional study was conducted from September 2015 to July 2016 in Isfahan, Iran. Participants were 150 students, aged 6-18 years, who were selected by multistage cluster random sampling from schools of Isfahan province. Blood and urine samples of participants were obtained for measurement of thyroid hormone levels (measured by immunoradiometric assay) and PAH urinary metabolites, including 1-hydroxynaphthalene, 2-hydroxynaphthalene, 9-hydroxyphenanthrene, and 1-hydroxypyrene. The association of serum thyroid-stimulating hormone (TSH) and PAH urinary metabolites was determined by correlation and regression analyses. Multivariate regression analysis revealed significant association between serum TSH and PAH urinary metabolites; this association remained significant after adjustment for gender and age. The corresponding figures were r = 0.85 for 1-naphthol, r = 0.86 for 2-naphthol, r = 0.87 for 1-hydroxypyrene, and r = 0.42 for 9-phenantrol, respectively, all p values < 0.001. The mean levels of 1-hydroxypyrene and 9-phenanthrol were higher in boys than those in girls (p < 0.05). The findings of this study indicated significant positive association between urinary PAH biomarkers and the TSH level in children and adolescents. It can be suggested that long-term exposure to PAHs might result in thyroid function impairment. The clinical implication of the current findings should be confirmed by future longitudinal studies.

Demographic and clinical characteristics of the children with aminoacidopathy in Isfahan Province, Central Iran in 2007-2015.

CONTEXT: Aminoacidopathies refer to defects in protein synthesis pathways which result in a range of biochemical disorders and clinical presentations. The enzyme defects in intermediate metabolic pathways lead to accumulation of one or more amino acids or metabolites. Despite higher prevalence rates, screening infants for inherited metabolic disorders is not run in many Middle East countries. AIM: This research is part of a larger study of inherited metabolic disorders to characterize and measure the prevalence of aminoacidopathies. SETTINGS AND DESIGN: Cross-sectional study in the population aged 0-17 years old in Isfahan province of Iran, 2007-2015. SUBJECTS AND METHODS: Demographic characteristics, history of disease, development of clinical condition and socioeconomic status were obtained from interviews as well as patient records of pediatric tertiary referral hospitals and metabolic disorders centers. STATISTICAL ANALYSIS USED: SPSS qualitative and quantitative analysis. RESULTS: The incidence rate of aminoacidopathies was derived to be 9/100,000 live births. The frequency of consanguineous marriages in this group of the patients was 89.2%. Of the patients with aminoacidopathies, 76.6% required hospitalization with tyrosinemia having the highest rate overall (>10 times). The most prevalent symptoms in this group of patients were developmental disorders and convulsions while half presented with growth disorders during follow-up. Of the 35.5% patients, who died at various ages, one-third was in the maple syrup urine disease subgroup. CONCLUSION: Although metabolic disorders are identified as rare diseases, they are more prevalent in the studied population of Isfahan.

Demographic and Clinical Findings in Pediatric Patients Affected by Organic Acidemia.

OBJECTIVE: Metabolic disorders, which involve many different organs, can be ascribed to enzyme deficiency or dysfunction and manifest with a wide range of clinical symptoms. This study evaluated some of the demographic and clinical findings in pediatric patients affected by organic acidemia. MATERIALS & METHODS: This cross-sectional study was part of a larger study conducted in patients with metabolic disorders during a period of 7 years from 2007 to 2014 in Isfahan Province, Iran. Our study covered a wide range of cases from newborn infants (one-week old) to adolescents (children up to the age of 17 years). This study evaluated patients' demographic information, history of disease, developmental and educational status, clinical and general conditions. Phone and in-person interviews were used to gather information. RESULTS: Out of 5100 patients screened in this study, 392 patients were affected by one of the different metabolic disorders and 167 individuals were diagnosed as organic acidemia. Propionic acidemia/methyl malonic acidemia (PA/MMA) was the most prevalent form of this metabolic disorder. The frequency of consanguinity was 84.7% in the group of patients. The mortality rate was 18.8% in patients with organic academia. CONCLUSION: Each of the metabolic diseases, as a separate entity, is rare; nevertheless, in aggregate they have a somewhat high overall prevalence. These diseases result in mental and developmental disorders in the absence of quick diagnosis and initiation of treatment. Furthermore, more mutations should be identified in societies affected by consanguinity. Further research should also be conducted to determine worthwhile and more-efficient screening methods as well as long term neurological prognosis.

Effect of folic acid on homocysteine and insulin resistance of overweight and obese children and adolescents.

BACKGROUND: Considering the increasing trend of childhood obesity and subsequent burden of the disease in Iran and other countries and importance of early life intervention for achieving sustained effect on health of children and adolescents, this study aimed to investigate the effect of two different dose of folic acid on homocysteine (Hcy) level and insulin resistance of obese children. MATERIALS AND METHODS: In this randomized, double-blind controlled clinical trial study, 60 obese and overweight children aged 5-12 years were enrolled. Selected obese children randomly allocated in two interventional (1 mg/day folic acid and 5 mg/day folic acid, for 8 weeks) and one control groups. Biochemical measurements including folic acid, Hcy, insulin and insulin resistance were measured between and within groups before and after trial. RESULTS: In each group, 20 obese children were studied. The three groups were age and sex matched. After folic acid administration, mean of Hcy, insulin resistance and insulin decreased significantly in two groups which folic acid administrated with two different doses (P < 0.05). The reduction in studied biochemical variables was similar in two interventional groups (1 and 5 mg folic acid daily) (P > 0.05). Mean differences for Hcy, insulin resistance and insulin, in two intervention groups were significantly higher than the control group (P < 0.0001). Mean differences of Hcy, insulin resistance and insulin, in two intervention groups were not different significantly (P > 0.05). CONCLUSION: The findings of current trial showed that folic acid in two studied doses could be a safe and effective supplement for obese children to reduce Hcy level and insulin resistance, which consequently could prevent obesity-related complications including cardiovascular and metabolic disorders.

Dietary Approaches to Stop Hypertension (DASH) Dietary Pattern Is Associated with Reduced Incidence of Metabolic Syndrome in Children and Adolescents.

OBJECTIVE: To assess the association of adherence to Dietary Approaches to Stop Hypertension (DASH)-style diet with development of metabolic syndrome (MetS) in children and adolescents. STUDY DESIGN: Dietary data were collected using a valid and reliable food frequency questionnaire among 425 healthy subjects, aged 6-18 years. MetS was defined as the presence of at least 3 of the following according to the Cook criteria: waist circumference ≥90th percentile for sex and age according to national reference curves; systolic blood pressure and/or diastolic blood pressure ≥90th percentile for sex, age, and height; fasting plasma glucose ≥100 mg/dL; triglycerides ≥110 mg/dL; and high-density lipoprotein cholesterol <40 mg/dL. The DASH-style diet score was assessed based on 8 components: high intakes of whole grain, vegetables, fruits, nuts, legumes; moderate amounts of low-fat dairy products; and low intake of red and processed meat, sweetened beverages, and sodium. Multivariable logistic regression models were used to estimate the OR and 95% CI after 3.6 years of follow-up for developing MetS in each quartile of DASH score after adjustment for baseline confounders. RESULTS: Mean ± SD for age and DASH score were 13.6 ± 3.7 years and 24.1 ± 4.3, respectively, at baseline. The OR (95% CI) of developing MetS in the highest, compared with the lowest, quartile of DASH score was 0.36 (0.14-0.94) with a linear decreasing trend (P for trend = .023). Also, incidence of hypertension, high fasting plasma glucose, and abdominal obesity decreased with higher adherence to DASH diet (P < .05 for all). CONCLUSIONS: Our findings indicate the relationship of adherence to DASH-style diet with MetS and some of its components in both children and adolescents.

Synthesis, radiolabeling and bioevaluation of a novel arylpiperazine derivative containing triazole as a 5-HT1A receptor imaging agents.

INTRODUCTION: It has been recognized that serotonin plays a main role in various pathological conditions such as anxiety, depression, aggressiveness, schizophrenia, suicidal behavior, panic and autism. 1-(2-Methoxyphenyl) piperazine pharmacophore, a fragment of the true 5-HT(1A) antagonist WAY100635, is found in numerous selective 5-HT(1A) imaging agents. In this paper, we have reported the synthesis of a novel derivative of 1-(2-methoxyphenyl) piperazine that is labeled with (99m)Tc (CO)(3) via click chemistry. METHODS: The bidentate alkyne, propargylglycine was reacted with phenyl piperazine triazole derivative in the presence of a catalytic amount of Cu (I) to form tridentate ligand. The ligand was radiolabeled with the precursor [(99m)Tc] [(H(2)O)(3) (CO)(3)](+) and characterized by HPLC. The bioevaluation of radio labeled ligand was carried out in rats. RESULTS: Triazole complex was labeled by (99m)Tc-tricarbonyl and its radiochemical yield was more than >95% which was determined by HPLC. In vivo stability studies in human serum albumin show a 93% ratio of complex after a 24h period. The calculated partition coefficient (logP) was 0.34±0.02. Receptor binding assays indicated about 70% specific binding of radioligand to 5-HT(1A) receptors. Biodistribution studies have shown brain hippocampus uptake of 0.40±0.08 %ID/g at 30 min post injection. CONCLUSIONS: Results indicate that this (99m)Tc-tricabonyl-arylpiperazine derivative has specific binding to 5-HT(1A) receptors and presented suitable characters for its use as a CNS imaging agent.

Clinical evaluation of antimicrobial peptide [(99m)Tc/Tricine/HYNIC(0)]ubiquicidin 29-41 as a human-specific infection imaging agent.

INTRODUCTION: Ubiquicidin (UBI) 29-41 is a cationic synthetic antimicrobial peptide fragment that binds preferentially with the anionic microbial cell membrane at the site of infection. This study was conducted to evaluate the potentiality of [(99m)Tc/Tricine/HYNIC(0)]UBI 29-41 prepared from lyophilized kits as an infection imaging agent in humans. METHODS: Seven patients (5 males and 2 females; mean age=55 years; age range=35-75 years) with suspected bone or soft-tissue infections participated in this study. [(99m)Tc/Tricine/HYNIC]UBI 29-41, corresponding to activity in the range 555-740 MBq added to 40 mug of peptide obtained from instant freeze-dried kit formulations with radiochemical purities >95%, was injected intravenously. A 45-min dynamic study was followed by spot views of the suspected region of infection (target) and a corresponding normal area (nontarget). Whole-body anterior and posterior images were also acquired at 30, 60 and 120 min after injection. True- or false-positive or true- or false-negative images were interpreted upon bacterial culture, radiography, clinical tests and bone scanning. RESULTS: The biodistribution of [(99m)Tc/Tricine/HYNIC]UBI 29-41 in patients showed rapid accumulation of activity in the kidneys in the first 30 min after injection that gradually declined and accumulated in the urinary bladder. There were positive findings in five studies and negative findings in two. Findings were subsequently confirmed to be true positive or negative. Images showed minimal accumulation in nontarget tissues, with an average target/nontarget ratio of 2.10+/-0.33 in positive lesions at 30 min. CONCLUSION: Given its favorable clinical characteristics, [(99m)Tc/Tricine/HYNIC]UBI 29-41 shows promise as a tracer for infection imaging that allows early diagnosis (30 min) of infection.

Preclinical evaluation of [99mTc/EDDA/tricine/HYNIC0, 1-Nal3, Thr8]-octreotide as a new analogue in the detection of somatostatin-receptor-positive tumors.

PURPOSE: Radiolabeled somatostatin analogues are important tools for the in vivo localization and targeted radionuclide therapy of somatostatin-receptor-positive tumors. The aim of this study was to evaluate a new somatostatin analogue designed for the labeling with (99m)Tc: [6-hydrazinopyridine-3-carboxylic acid (HYNIC(0)), 1-Nal(3), Thr(8)]-octreotide ([HYNIC]-NATE), using ethylenediamine-N,N'-diacetic acid (EDDA) and tricine as coligands. METHODS: Synthesis was preformed on a solid phase using a standard Fmoc strategy. Labeling with (99m)Tc was performed at 100 degrees C for 10 min using SnCl(2) as a reductant. Radiochemical analysis involved ITLC and high-performance liquid chromatography methods. Peptide conjugate affinity was determined in AR4-2J cell membranes. The internalization and externalization rates were studied in sstr(2)-expressing AR4-2J cells. Biodistribution of radiopeptide was studied in rats bearing the AR4-2J tumor. RESULTS: Radiolabeling was performed at high specific activities, and radiochemical purity was >95%. Peptide conjugate showed high affinity binding for sstr(2). The radioligand showed a moderate and specific internalization into AR4-2J cells (14.13+/-0.61% at 4 h). In animal biodistribution studies, a receptor-specific uptake of radioactivity was observed in somatostatin-receptor-positive organs. After 4 h, uptake in the AR4-2J tumor was 1.33+/-0.23%ID/g (percentage of injected dose per gram of tissue). CONCLUSION: These data show that [(99m)Tc/EDDA/tricine/HYNIC]-NATE is a specific radioligand for the somatostatin-receptor-positive tumors and is a suitable candidate for clinical studies.

Congenital hypothyroidism in Iran.

OBJECTIVE: Following elimination of iodine deficiency in Iran, the program of screening for congenital hypothyroidism (CH) was established in 1998. The descriptive findings of the study are reported here. METHODS: From February 1998 to June 2001, cord blood spot samples from 8 hospitals and a rural birth center in Tehran and Damavand were collected and tested for TSH measurement using a two-site IRMA method. TSH values > or = 20 microU/mL were recalled. The diagnosis of CH was confirmed using age adjusted reference values for serum TSH and T4 levels. RESULTS: Of 20107 screened neonates, 256 had cord TSH values > or = 20 microU/mL (recall rate: 1.3%) and 22 showed hypothyroidism (1:914 live births). History of maternal ingestion of drugs and dietary goitrogens were negative and minimal, respectively. 15 out of 21 CH neonates had parental consanguinity. The odds ratio of CH occurrence in blood-related to non-related marriages was 6.9 (CI=1.82-25.87). Thyroid dysgenesis occurred in 10 neonates; 1:2011 births. Urinary iodine excretion was between 12-22 (n=3) and 40-42.5 (n=5) microg/dL in 10 eutopic neonates (2 not assessed). CONCLUSION: Parental consanguinity and iodine excess could be the causative factors for the high incidence of CH.