morteza pourfarzam

Trace elements deficiency is common among end‑stage renal disease (ESRD) patients due to excessive loss during dialysis and the lower intake secondary to loss of appetite. Selenium (Se) is a trace element that plays an important role in the radical scavenging system and helps the body defend against oxidative stress. This study aims to evaluate the effects of Se supplementation on lipid profile, anemia, and inflammation indices in ESRD patients.

Fifty‑nine hemodialysis patients enrolled and were randomly divided into two groups. Two hundred microgram Se capsules once daily for the case group and matching placebo for the control group were administered for three months. Demographic data were collected at the study beginning. Uric acid (UA), anemia and inflammation indices, and lipid profiles were recorded at the beginning and the end of the study.

UA and UA‑to‑HDL (high‑density lipoprotein) ratio decreased significantly in the case group (P < 0.001). The changes in lipid profile were not significant among both groups. Hemoglobin slightly increased in the case group, however, it decreased significantly in the control group (P = 0.031). High‑sensitivity C‑reactive protein (hs- CRP) decreased in the case group and increased in the control group, however, none of these changes were significant.

According to the results of this study, selenium supplementation in ESRD patients could reduce some risk factors related to their mortality, such as the ratio of uric acid to HDL. However, the changes related to lipid profile, hemoglobin level and hs-CRP biomarker were not significant.

One of the most common diseases with high morbidity and mortality rates is chronic kidney disease. Cardiovascular disease affects most patients with chronic kidney disorders, particularly patients undergoing dialysis; hence, appropriate prevention and management approaches are essential. This study aimed to evaluate the reduction of inflammatory biomarkers, especially homocysteine, by omega-3 fatty acids in peritoneal dialysis patients.

This study enrolled 60 peritoneal dialysis patients who met specified inclusion and exclusion criteria and were randomized to intervention or placebo groups. Omega-3 capsules were given at a dose of 3 g/d for 8 weeks. Inflammatory markers, including high‑sensitivity C‑reactive protein (hs‑CRP), homocysteine, albumin, and lipid profile measured before and after the study.

Results of this trial revealed that the levels of homocysteine, hs‑CRP, and albumin did not change significantly during the study. Analysis of lipid profiles before and after intervention showed omega‑3 has no significant effect on the level of total cholesterol or low‑density lipoprotein cholesterol; However, the level of triglyceride reduced remarkably (P = 0.002). In addition, serum levels of high-density lipoprotein cholesterol increased at the end of the study (P < 0.001).

Omega-3 does not seem to be able to change the inflammatory markers significantly, particularly homocysteine. More extensive trials must be conducted to better understand the impact of omega-3 on inflammatory and nutritional markers, particularly in peritoneal dialysis patients.

Trace element deficiency is common among patients with end‑stage renal disease (ESRD); the reason is that since these patients undergo dialysis, they lose these elements more than healthy people, and also the use of trace elements is restricted due to loss of appetite. Selenium (Se) is a trace element that is essential for the oxidative stress defense system. Se deficiency leads to some complications similar to those often seen in ESRD patients, such as all-cause mortality due to cardiovascular diseases, bone loss, uric acid elevation, and anemia. This article aims to review the evidence on consequences of Se deficiency in ESRD patients, as well as effects of Se supplementation in hemodialysis patients. Multiple databases were searched to summarize the available evidence on selenium’s role in kidney diseases. Since the complications of ESRD and those of Se deficiency are mostly similar, this triggers the idea that Se deficiency may be considered as a cause of these problems, but it needs to be more assessed that Se deficiency is a single factor or there are other factors participated in. Also the role of Se supplementation on resolving the mentioned complications, needs to be more studied through welldesigned clinical studies.

MicroRNAs (miRNAs) are small non-coding RNA molecules acting as critical regulators of post-transcriptional gene expression. MiR-33a and miR-122 have a crucial role in cholesterol and lipid metabolism. Therefore, their dysregulation may contribute to metabolic abnormality and their inhibition may be a useful therapeutic strategy. The objective of the present study was to investigate the relationship between miR-33a, miR-122, erythrocyte membrane fatty acids profile, and serum lipids with components of metabolic syndrome in an Iranian population suffering from type 2 diabetes mellitus (T2DM).

 Expression of miR-33a and miR-122 was measured by real-time polymerase chain reaction and erythrocyte membrane fatty acid pr ofiles were analyzed by gas chromatography-mass spectrometry.

T2DM patients with and without metabolic syndrome had significantly higher miR-33a and miR-122 levels compared to controls. MiRNAs were significantly correlated with saturated fatty acid (SFAs), total SFAs/total polyunsaturated fatty acids (PUFAs) ratio, fasting plasma glucose, triacylglycerols, insulin and homeostatic model assessment of insulin resistance. In addition, there was a significant negative correlation between miR-33a and miR-122 levels and PUFAs, total PUFAs/total SFAs ratio and omega 6 fatty acids.

Considering the roles of miR-33a and miR-122 in cholesterol and lipids metabolism, it may be concluded that the measurement of their expression may be useful as a potential additional biomarker for cardiometabolic derangement in T2DM patients. In addition, these findings may suggest that the inhibition of these miRNAs by anti- miRNA therapies may be explored as a potential therapeutic strategy.

The incidence of cardiovascular events and mortality is higher in patients with chronic kidney disease (CKD) compared to the general population. Homocysteine (Hcy) appears to be an independent risk factor for cardiovascular diseases in general populations and patients with CKD. Further, hyperhomocysteinemia can cause endothelial damage and increase the activity and production of coagulation factors, and its prevalence among patients with end‑stage renal disease is approximately 85%–100%. Most treatments, which lower Hcy levels and have been considered in previous studies, include folic acid, B vitamins, omega‑3 fatty acids, and N‑acetylcysteine. However, the effect of therapies that can decrease Hcy levels and thus cardiovascular events in these patients is still unclear. The results are conflicting and require further investigation. To guide treatment decisions and improve patient outcomes, multiple databases were searched, including Web of Science, PubMed, and Medline to summarize the available evidence (i.e., clinical trial and meta-analyses) on Hcy-lowering interventions and cardiovascular events.

Imbalance in blood levels of trace elements is independent risk factor for metabolic syndrome (MetS), type 2 diabetes mellitus (T2DM), and its complications. This study investigated plasma and erythrocyte levels of copper, magnesium, zinc, and their correlations with biochemical components of the MetS in T2DM patients compared to the healthy controls.

Forty men recently diagnosed T2DM with MetS without complications and thirty six age-matched healthy controls were enrolled in this cross-sectional study. Plasma and erythrocyte levels of selected elements were measured by graphite furnace atomic absorption spectroscopy.

The results of the present study showed significantly lower plasma levels of copper, magnesium, and zinc and lower erythrocytes copper in the patients' group compared to the controls; while erythrocyte levels of magnesium and zinc were not significantly different between the two groups. Significant negative correlations were observed between plasma levels of copper with waist and hip circumferences, waist to hip ratio, systolic and diastolic blood pressures, fasting blood glucose, and glycated hemoglobin levels in all subjects; while erythrocyte copper levels showed significant negative correlation with triglyceride, and erythrocyte zinc was positively correlated with diastolic blood pressure and negatively with triglyceride.

Alterations of trace elements may have a significant role in the pathogenesis of MetS and T2DM patients. It is suggested that the body status of copper, magnesium, and zinc might be significantly correlated with components of MetS in T2DM patients; and plasma copper levels may be correlated with complications of type 2 diabetes mellitus.

Background:

The concurrence of metabolic syndrome (MS) and diabetes mellitus (DM) is increasing worldwide. The long‑term complications of these chronic diseases are a threat to patients’ well‑being. Oxidative stress is involved in the pathogenesis of several diseases. To understand the basic pathophysiological mechanisms of Type‑2 DM (T2DM) and its related complications, we aimed to investigate the oxidant/antioxidant status and Na+‑K+ ATPase activity in T2DM with MS.

Materials and Methods:

A population of ninety individuals including fifty patients diagnosed with T2DM and MS, but without overt diabetes complications, and forty individuals without T2DM or MS as control group participated in this study. Plasma malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) activities, total antioxidant capacity (TAC), and Na+‑K+ ATPase activity were assessed by standard laboratory methods. Results Plasma MDA in patients group was statistically significantly higher than that of controls (P ≤ 0.05). Whereas, Na+‑K+ ATPase activity was statistically significantly lower in patient group (P ≤ 0.05). TAC, CAT, SOD, and GPx enzyme activities were not statistically significantly different between two groups (P > 0.05).

Results: 

from the patient group showed positive correlations between CAT activity and triglyceride and positive correlations between GPx activity and weight, body mass index (BMI), and waist circumference. In addition, there was a positive correlation between MDA results with high‑density lipoprotein‑cholesterol (HDL‑C) and total cholesterol and a negative correlation with TAC, BMI, and weight (P ≤ 0.05) in controls.

Conclusion: 

Because T2DM patients were without any vascular complications, antioxidant defense results may reflect the lack of progression of diabetes complications in these patients. These results emphasize the need for initial and continued assessment of cardiovascular disease risks in diabetic individuals. Implementation of timely interventions may improve the management of diabetes and prevent the progression of diabetes complications.

Reteplase, the recombinant form of tissue plasminogen activator, is a thrombolytic drug with outstanding characteristics, while demonstrating limited solubility and reduced plasminogen activation. Previously, we in silico designed a variant of Reteplase with positively supercharged surface, which showed promising stability, solubility and activity. This study was devoted to evaluation of the utility of supercharging technique for enhancing these characteristics in Reteplase. To test the hypothesis that reinforced surface charge of a rationally-designed Reteplase variant will not compromise its stability, will increase its solubility, and will enhance its plasminogen cleavage activity. Supercharged Reteplase coding sequence was cloned in pDest527 vector and expressed in E. coli BL21 (DE3). The expressed protein was extracted by cell disruption. Inclusion bodies were solubilized using guanidine hydrochloride, followed by dialysis for protein refolding. After confirmation with SDS-PAGE and western blotting, extracted proteins were assayed for solubility and tested for bioactivity. SDS-PAGE and western blot analysis confirmed the successful expression of Reteplase. Western blot experiments showed most of Reteplase expressed in the insoluble form. Plasminogen cleavage assay showed significantly higher activityof the supercharged variant than the wild type protein (P < 0.001). The stability of the supercharged variant was also comparable to the wild type. Our findings, i.e. the contribution of the surface supercharging technique to retained stability, enhanced plasminogen cleavage activity, while inefficiently changed solubility of Reteplase, contain implications for future designs of soluble variants of this fibrinolytic protein drug.

Reteplase (recombinant plasminogen activator, r-PA) is a thrombolytic agent recombined from tissue-type plasminogen activator (t-PA), which has several prominent features such as strong thrombolytic ability and E. coli</em> expressibility. Despite these outstanding features, it demonstrates reduced fibrin binding affinity, reduced stimulation of protease activity, and lower solubility, hence higher aggregation propensity, compared to t-PA. The present study was devoted to design r-PA variants with comparable structural stability, enhanced biological activity, and high solubility. For this purpose, computational molecular modeling techniques were utilized. The supercharging technique was applied for r-PA to designing new species of the protein. Based on the results from in silico</em> evaluation of selected mutations in comparison to the wild-type r-PA, the designed supercharged mutant (S7 variant) exhibited augmented stability, decreased solvation energy, as well as enhanced binding affinity to fibrin. The data also implied increased plasminogen cleavage activity of the new variant. These findings have implications to therapies which involve removal of intravascular blood clots, including the treatment of acute myocardial infarction.

Nowadays, coronary artery diseases (CADs) are among the most common diseases in societies. The aim of this study was to study the interplay between cholesterol absorption and synthesis in two groups of Iranian patients with CAD by measuring the markers of cholesterol synthesis and absorption pathways in plasma.

The study population included 128 patients undergoing clinically indicated coronary angiography. Patients were divided into two groups after scoring the severity of their coronary stenosis; the S-stenosis group (patients with CAD, n = 75) had a significant stenosis indicated by coronary angiography, and the second group, N-stenosis (n = 55), had no significant coronary stenosis. Fasting plasma samples were used to measure cholesterol absorption and synthesis markers by gas chromatography-mass spectrometry (GC-MS).

The level of cholesterol absorption markers in patients with coronary artery stenosis was slightly increased compared to patients without coronary artery stenosis, but this change was statistically significant only for cholestanol (P < 0.050). In terms of cholesterol synthesis markers, the results did not show any significant differences between the two groups (P > 0.050 for all).

Study of cholesterol synthesis and absorption markers has not been reported in Iranian patients before. This article reports the results of such study for the first time. Considering the high prevalence of CADs and the importance of cholesterol metabolism in pathology of these diseases, the results may be used to understand some underlying mechanisms of development and progression of these diseases, and to manage the patient better.

Type 2 diabetes mellitus (T2DM) is the most common form of diabetes caused by insufficient insulin secretion, insulin resistance, or both. Considering the high prevalence of T2DM, and the role of various components in the progress of the disease, and in order to better understand some of the mechanisms of pathogenesis responsible for the progression of T2DM, this study aimed to investigate if the levels of cholesterol synthesis and absorption markers in patients with T2DM was different compared with healthy subjects. In this cross-sectional study, 150 men between 40 and 60 years of age were selected from people attending Isfahan diabetes centers and the Isfahan Endocrine and Metabolism Research Center, Isfahan, Iran. The subjects were divided into control group including 50 apparently healthy men with normal fasting blood glucose (FBG) and no history of T2DM, and 100 patients with FBG ≥ 126 mg/dl and a history of T2DM. Fasting serum and plasma samples were used to measure biochemical parameters using commercial laboratory methods, and absorption and synthesis markers of cholesterol, using gas chromatography-mass spectrometry technique. Statistical analyzes were done via SPSS software using Kolmogorov-Smirnov, independent t, and Mann-Whitney tests at the significance level of P < 0.05. There were significant differences in the biochemical and anthropometric parameters between the studied groups. Evaluation of the concentration ratio of absorption (β-sitosterol and campesterol) and synthesis (lathosterol and desmosterol) markers to cholesterol showed a significant increase in the synthesis markers, and a significant decrease in the absorption markers in the patients group compared to the control group (P < 0.05). The results of this study indicate that the rate of cholesterol synthesis is increased, and that of cholesterol absorption is decreased in a population of Iranian patients with T2DM. These findings are in accordance with data from other populations, and may indicate that the cholesterol synthesis and absorption markers may be used as surrogate markers to better understand some of the pathogenesis mechanisms involved in the development and complications of T2DM, and may help to predict, and treat its complications more effectively in the future.

In this study, we investigated the associations of erythrocytes fatty acid composition, activities of delta?5 desaturase (D5D) and delta?6 desaturase (D6D), and other metabolic risk factors, with type 2 diabetes (T2D) risk to determine if rs174583 polymorphism of FADS2 gene had any e?ect on these associations.
Fatty acid profle of erythrocytes was determined using gas chromatography?mass spectrometry in 95 T2D patients and 95 apparently healthy participants. Te genotypes of single?nucleotide polymorphism (SNP) of FADS2 gene were determined using the polymerase chain reaction?restriction fragment length olymorphism technique. Other biochemical parameters were measured in the serum using standard analytical procedures.
D6D activity was increased (P In the population studied, there was a strong association in the erythrocytes fatty acid composition, D5D and D6D activities and other metabolic risk factors between non?T2D and T2D patients. In addition, there was a strong association in erythrocytes DGLA and AA contents and D5D activities between rs174583 genotypes in all participants. However, the distribution of rs174583 genotypes did not di?er signifcantly between T2D patient and controls, and it did not appear to be an association between rs174583 SNP and incident of T2D.

Insulin resistance (IR) is associated with low‑grade systemic inflammation. It plays an important role in the pathogenesis of type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD) in patients with metabolic syndrome (MetS). It is unclear whether diabetic patients with MetS confer elevated CVD risk and outcomes beyond the impact of individual’s components of MetS. The aim of this study is to highlight the central role of IR, inflammation, triglyceride/high‑density lipoprotein‑ cholesterol (TG/HDL‑C) ratio, and atherogenic index of plasma (AIP) in T2DM with MetS.

This cross‑sectional study comprised 130 men distributed into three groups, namely Controls: 40 nondiabetic healthy volunteers; Group I: 40 T2DM patients without MetS, and Group II: 50 T2DM patients with MetS. Fasting blood samples were collected for the measurement of blood lipid profile, glucose, insulin, hemoglobin A1c, and high‑sensitivity C‑reactive protein (hs‑CRP). TG/HDL‑C ratio, AIP, and homeostasis model assessment of insulin resistance (HOMA-IR) were calculated.

Significant positive association was observed between HOMA‑IR and hs‑CRP only in Group II and between HOMA‑IR and TG/HDL‑C ratio in all subjects. Significant differences were seen in waist and hip circumferences, waist/hip ratio, body mass index, systolic blood pressure, fasting blood glucose, TGs, HDL‑C, insulin, hs‑CRP, HOMA‑IR, TG/HDL ratio, and AIP between Controls and Group I with Group II.

In T2DM with MetS, coexistence of elevated atherogenic indices, systemic inflammation, and association between HOMA‑IR and TG/HDL‑C ratio were seen. These factors are considered having important role in elevated CVD risk beyond MetS components in these patients.

Diabetes is the 6th leading cause of death and nowadays much efforts are done to identify the influential factors in creation of diabetes. The aim of this study was to investigate the relationship between blood concentration of Chromium and Vanadium in metabolic syndrome (MetS) subjects with or without type 2 diabetes (T2D).
Blood samples from subjects digested in nitric acid. The concentration of Chromium and Vanadium in MetS group with T2D 47 patients (30 women, 17 men) and MetS group without T2D 45 patients (33women 12 men) plus normal group 35 person (23 women 12 men) were measured by Furnace Graphite Flameless Atomic Absorption instrument.
The results of Cr and V measurements in blood subjects indicated that there are significant differences between the two groups (p The results of this study indicated that the blood level of measured elements has a correlation with diabetes and metabolic syndrome. Therefore, by measuring the elements level for providing them as a supplements to prevent from the ongoing of the disease or its progress.

Tyrosinase is a key enzyme in pigment synthesis. Overproduction of melanin in parts of the skin results in hyperpigmentation diseases. This enzyme is also responsible for the enzymatic browning in fruits and vegetables. Thus, its inhibitors are of great importance in the medical, cosmetic and agricultural fields.
A series of twelve kojic acid derivatives were designed to be evaluated as tyrosinase activity inhibitors. The potential inhibitory activity of these compounds was investigated in silico using molecular docking simulation method. Four compounds with a range of predicted tyrosinase inhibitory activities were prepared and their inhibitory effect on tyrosinase activity was evaluated. The antioxidant properties of these compounds were also investigated by in vitro DPPH (2,2-diphenyl-1-picrylhydrazyl) and hydrogen peroxide scavenging assays.
Compound IIId exhibited the highest tyrosinase inhibitory activity with an IC50 value of 0.216 ± 0.009 mM which was in accordance with the in silico ΔGbind results (-13.24 Kcal/mol).
Based on the docking studies, from the twelve compounds studied, one (IIId) appeared to have the highest inhibition on tyrosinase activity. This was confirmed by enzyme activity measurements. Compound IIId has an NO2 group which binds to both of Cu2 ions located inside the active site of the enzyme. This compound appeared to be even stronger than kojic acid in inhibiting tyrosinase activity. The DPPH free radical scavenging ability of all the studied compounds was more than that of BHT. However, they were not as strong as BHT or gallic acid in scavenging hydrogen peroxide.

Multiple factors are involved in the development and progression of type 2 diabetes mellitus (DMII) to DMII with metabolic syndrome (MetS) and cardiovascular complications. To identify some of these factors, we aim to investigate the changes in erythrocyte membrane Na+/K+-ATPase activity, serum glucose, insulin, lipid profi le, hemoglobin A1C (HbA1c), high-sensitivity C-reactive protein (hs-CRP), anthropometric measurements, and blood pressure in DMII with and without MetS. Th is cross-sectional study comprised 155 male subjects distributed into three groups as healthy controls (50 non-DMII volunteers), Group I (50 DMII without MetS), and Group II (55 DMII with MetS). Fasting blood samples were taken for the measurement of glucose, insulin, HbA1c, hs-CRP and lipid profi le. Na+/K+-ATPase activity was determined in erythrocyte ghost. Na+/K+-ATPase activity was signifi cantly decreased in DMII groups compared with controls. No signifi cant diff erence was shown in Na+/K+-ATPase activity between DMII groups. Total ATPase activity, total cholesterol and low-density lipoproteincholesterol levels were similar in the three groups. Levels of insulin, hs-CRP, triacylglycerols, systolic blood pressure, weight, waist and hip circumference, waist/hip ratio, and body mass index were signifi cantly elevated and high-density lipoprotein-cholesterol signifi cantly decreased only in Group II. Signifi cant diff erences in serum glucose and hip circumference were seen between the groups. No signifi cant diff erences in HbA1c levels were observed between DMII groups. Changes in many of the measured risk factors that occurred only in Group II compared with controls and Group I may provide an explanation of how DMII progresses to DMII with MetS and future cardiovascular complications.

The influence of vitamin D receptor (VDR) gene polymorphisms on the regulation of the parathyroid hormone is important in end-stage renal disease (ESRD) patients. We analyzed rs1544410 (BsmI) and rs731236 (TaqI) polymorphisms of VDR gene in hemodialysis patients to determine their relationship with serum intact parathyroid hormone (iPTH).

Ninety hemodialysis patients were included in this study. Patients were classified into four groups according to their serum iPTH level. Polymorphisms of VDR gene were surveyed using polymerase chain reaction-restriction fragment length polymorphism method with BsmI and TaqI enzymes in all the patients.

Patients age ranged between 30 and 60 years (mean ± SD: 36.0 ± 11.4) and period undergoing hemodialysis 80 ± 71 months. Patients were divided into four groups based on the serum concentration of iPTH. The distribution of VDR gene allelic variation for BsmI and TaqI polymorphisms was different between the four groups of uremic patients. Analysis of data revealed a significant correlation between the TaqI variants and serum iPTH level. There was also a correlation between the BsmI variants and serum iPTH level in that patients with the BB genotype were more likely to have a higher serum iPTH level. However, the latter was not statistically significant.

Genotype of the TaqI and BsmI VDR gene polymorphisms is reported in Iranian patients with ESRD. Those with tt or BB genotypes may develop more severe secondary hyperparathyroidism.

Organic acidurias are a heterogenous group of inherited metabolic disorders characterized by the accumulation and urinary excretion of organic acids. Delay in the detection and treatment of many of these disorders may lead to permanent brain damage or death. Accurate and early diagnosis is therefore paramount. The diagnosis of these disorders is achieved by the analysis of organic acids in the urine using gas chromatography/mass spectrometry (GC/MS). Since genetic and environmental factors and feeding habits can affect the concentration and profile of organic acids, for each population, data should be collected appropriate to that population. Such data did not exist for the Iranian population and thus, needed to be collected. 140 random urine samples were collected from healthy children in 4 age groups: term neonates (< 30 days), premature neonates, infants (1 month-2 years), and children (> 2 years). In addition, urine samples were collected from 10 children with classical symptoms of inherited metabolic disorders. After extraction and preparation of trimethylsilyl derivatives, organic acids were analyzed using GC/MS. 61 organic acids in 140 healthy urine samples were measured and the results were reported as the 2.5th-97.5th percentiles. These compounds were normal components of urine and some marker of diseases. In addition, among 10 samples collected from patients suspected of a metabolic disease, 2 patients with methyl malonic academia, 1 patient with propionic acidaemia and 1 patient with glutaric academia type 2 were identified. Urinary organic acid analysis is not currently performed in Iran and samples are sent abroad for investigation. In addition, no reference ranges for urinary organic acids in healthy Iranian children is available. This article, for the first time, reported the urinary organic acid analysis using GC/MS and reference ranges for the Iranian population. Urinary organic acids can now be analysed and results become available within the same day of patient admission in order to initialize early and targeted treatment. This study shows that metabolic disorders do exist in high proportion of patient with clinical signs and it appears that these diseases are prevalent. It also seems that methyl malonic acidemia is the most common disorder in patient with classic symptoms of organic acidemia in Iran.

Newborn screening is important for the early detection of many congenital genetic and metabolic disorders, aimed at the earliest possible recognition and management of affected newborns, to prevent the morbidity, mortality, and disabilities associated with an inherited metabolic disorder. This comprehensive system includes; testing, education, follow up, diagnosis, treatment, management, and evaluation. There are major differences among many of the disorders being considered for inclusion in newborn screening programs. In recent times, advances in laboratory technology such as tandem mass spectrometry (MS/MS), which is more specific, sensitive, reliable, and comprehensive than traditional assays, has increased the number of genetic conditions that can be diagnosed through neonatal screening programs at birth. With a single dried filter paper blood spot, MS/MS can identify more than 30 inherited metabolic disorders in around two to three minutes. Advances in the diagnosis and treatment and an increased understanding of the natural history of inborn errors of metabolism have produced pressure to implement expanded newborn screening programs in many countries. Even as many countries throughout the world have made newborn screening mandatory, in Iran, nationwide newborn screening for inherited metabolic disorders other than hypothyroidism has not been initiated, hence, there is little information about these diseases. This article aims to review the recent advances in newborn metabolic screening and its situation in Iran and other countries.

Renal osteodystrophy is a common finding in patients with chronic kidney disease (CKD) requiring dialysis (stages 3-5). Increased serum activity of bone isoform alkaline phosphatase is a good marker for investigating uremic osteodystrophy in these patients. Considering the important effect of vitamin D on calcium، mineral homeostasis and parathyroid hormone (PTH)، the objective of this study was investigation of association between serum levels of PTH، 25 (OH) D3، Alkaline phosphatase (ALP)، calcium (Ca) and inorganic phosphate (Pi) in hemodialysis patients.

Ninety hemodialysis patients were included in this study. Mean age of the patients was 36. 0 ± 11. 4 years and duration of receiving dialysis was 2 months to 23 years (Mean ± SD: 80 ± 71 months). The serum levels of 25 (OH) D3، ALP، Ca and Pi and PTH were measured. Data analysis was performed using SPSS software.

Abnormal levels of serum Ca and Pi were more common in men than women (Ca: 63. 6% versus 52. 8%، Pi: 72. 7% versus 50%، in men and women respectively); but more women had abnormal serum levels of ALP، PTH and vitamin D compared to men (ALP: 75% versus 54. 5%، PTH: 97. 2% versus 94. 5%، 25(OH) D3:63. 9% versus 32. 7%، in women and men respectively). Statistical correlation between serum levels of ALP and PTH (P = 0. 0500)، PTH and hemodialysis duration (r = 0. 588، P < 0. 0005) were significant. No statistically significant correlation was observed between serum levels of PTH and other biochemical factors.

In the majority of studied patients، the serum Pi and PTH levels were out of normal ranges that indicate poor management of hyperparathyroidism and Pi in these patients. According the results of this study، the intensity of secondary hyperparathyroidism and its deleterious effects on bone tissue was more common in women than men.

Organic acidurias (or organic acidemias) are a group of inherited metabolic disorders usually caused by loss or lack of the activity of one enzyme in the catabolic pathway of amino acids، fatty acids، carbohydrates، cholesterol، biogenic amines، nucleic acids، and steroids. Accurate and early diagnosis and follow-up of these disorders are very important in prevention of permanent damage of the nervous system، mental retardation، and death. Pathological changes in normal catabolism of these compounds are usually reflected in patient''s urinary organic acid profile. These changes can be identified by analysis of urinary organic acids using gas chromatography-mass spectrometry (GC-MS). Since each disease usually has a unique profile، the disorders can be identified by this method. The analysis of urinary organic acids is not currently performed in Iran and samples are sent abroad for such evaluations. However، timely diagnosis and follow-up of these disorders requires accurate determination of normal ranges and profile of urinary organic acids in healthy populations. Genetic and environmental factors and dietary habits can affect the concentration of urinary organic acids. Therefore، data about each population has to be collected separately. The absence of such data in Iran necessitates assessments in the country.

High density lipoprotein (HDL) particles are heterogeneous in composition, structure, size, and may differ in conferring protection against cardiovascular disease. HDL associated enzyme, paraoxonase-1 (PON1), has an important role in attenuation of atherogenic low density lipoprotein (LDL) oxidation. The aim of this study was to investigate the associations between HDL particle size and PON1 activity in relation to serum HDL cholesterol (HDL-C) levels. One hundred and forty healthy subjects contributed to this study. HDL was separated by sequential ultracentrifugation and its size was estimated by dynamic light scattering. Paraoxonase activity was measured spectrophotometrically using paraoxon as substrate. Results of this study showed that PON1 activity had negative correlations with HDL mean particle size (r = −0.22, P < 0.01), HDL2/HDL3 ratio, and serum HDL-C levels (r = −0.25, P < 0.01). HDL mean particle size and HDL2/HDL3 ratio had negative correlation with body mass index (BMI), waist hip ratio (WHR), and serum triglyceride (TG) levels, and positive correlation with serum HDL-C levels. Serum HDL-C levels had significant positive correlations with age, total cholesterol (TC), and apolipoprotein A-I (apo A-I) and significant negative correlation with BMI, WHR, and TG. Based on the results of this study, determination of HDL mean particle size beside the serum PON1 activity may help to better understand the CAD risks, pathogenesis, and prognosis, and may also help to design therapeutic protocols toward beneficial modifications of HDL characteristics.

Platelet-activating factor acetylhydrolase (PAF-AH) is a circulating enzyme that has an important role in the development of coronary artery disease (CAD). The correlations between PAF-AH and CAD are controversial. Furthermore, the differences of the enzyme levels between patients with stable and unstable CAD are not fully determined. The purpose of this study was to evaluate plasma PAF-AH levels and its association with the presence of CAD and some clinical risk factors in the patients. This case-control study included 50 control subjects without CAD, 50 stable CAD patients and 50 unstable CAD patients with angiographically documented CAD. Plasma PAF-AH activity was determined by a commercial kit. The inflammatory markers, high sensitivity C-reactive protein (hsCRP) and oxidized low density lipoprotein (ox-LDL), and lipid profile were also measured. Comparisons of biochemical risk factors among all groups were performed by one way ANOVA. The association of PAF-AH activity with the presence of CAD was analyzed by multiple logistic regression. Plasma PAF-AH activity levels were higher in unstable CAD patients (0.040 ± 0.012 μmol/min/mL) than in stable CAD patients (0.032 ± 0.010 μmol/min/mL) and control subjects (0.026 ± 0.009 μmol/min/mL) (p < 0.01). Plasma PAF-AH activity was also independently associated with the presence of CAD (p < 0.01). Plasma PAF-AH activity levels were highly increased in unstable and stable CAD patients as compared to control subjects and may be a useful biomarker for CAD prediction.