How much obesity and diabetes do impair male fertility?

BACKGROUND: Subfertility in obese and diabetic men during the reproductive age is evident, but the mechanisms by which obesity and diabetes mellitus cause male infertility are not entirely understood. The current study aimed to evaluate the effects and potential mechanisms of obesity and diabetes on male fertility. METHODS: We enrolled control = 40, obese = 40, Lean-DM = 35, and Obese-DM = 35 individuals. The obesity-associated markers, diabetic markers, hormonal and lipid profile, inflammatory indices, and semen analysis were assessed in four experimental groups. RESULTS: Our finding showed that diabetic markers were significantly increased in two diabetic groups, while obesity indices were markedly increased in two obese groups. Conventional sperm parameters were significantly lower in three groups compared with the control. Serum levels of total testosterone and sex hormone-binding globulin were significantly lower in men with obesity and DM compared with the control. There was a significant difference in the concentration of high-sensitivity C-reactive protein among four experimental groups. Moreover, serum leptin was significantly increased in obese DM, lean DM, and obese groups. Serum insulin levels had a positive correlation with metabolic-associated indices and high-sensitivity C-reactive protein levels, whereas it had a negative correlation with count, motility, and morphology. CONCLUSIONS: Our findings showed the metabolic changes, hormonal dysfunction and inflammatory disturbance might be suspected mechanisms of subfertility in obese and diabetic subfertile men.

Nuclear Factor Kappa-B Protein Levels in Sperm of Obese Men with and without Diabetes; Cellular Approach in Male Infertility.

OBJECTIVE: Although the role of obesity and diabetes mellitus (DM) in male infertility is well established, little information about the underlying cellular mechanisms in infertility is available. In this sense, nuclear factor kappa-B (NF-kB) has been recognized as an important regulator in obesity and DM; However, its function in the pathogenesis of male infertility has never been studied in obese or men who suffer from diabetes. Therefore, the main goal of current research is assessing NF-kB existence and activity in ejaculated human spermatozoa considering the obesity and diabetics condition of males. MATERIALS AND METHODS: In an experimental study, the ELISA technique was applied to analyze NF-kB levels in sperm of four experimental groups: non-obese none-diabetic men (body mass index (BMI) <25 kg/m2; control group; n=30), obese non-diabetic men (BMI >30 kg/m2; OB group; n=30), non-obese diabetic men (BMI <25 kg/m2; DM group; n=30), and obese diabetic men (BMI >30 kg/m2; OB-DM group; n=30) who were presented to Royan Institute Infertility Center. In addition, protein localization was shown by Immunocytofluorescent assay. Sperm features were also evaluated using CASA. RESULTS: The diabetic men were older than non-diabetic men regardless of obesity status (P=0.0002). Sperm progressive motility was affected by obesity (P=0.035) and type A sperm progressive motility was affected by DM (P=0.034). The concentration of sperm (P=0.013), motility (P=0.025) and morphology (P<0.0001) were altered by obesity × diabetes interaction effects. The NF-kB activity was negatively influenced by the main impact of diabetics (P=0.019). Obesity did not affect (P=0.248) NF-kB activity. Uniquely, NF-kB localized to the midpiece of sperm and post-acrosomal areas. CONCLUSION: The current study indicated a lower concentration of NF-kB in diabetic men, no effect of obesity on NF-kB was observed yet. Additionally, we revealed the main obesity and diabetes effects, and their interaction effect adversely influenced sperm characteristics.

Early Postpartum Glucose Intolerance, Metabolic Syndrome and Gestational Diabetes Mellitus Determinants after Assisted Conception: A Prospective Cohort Study.

BACKGROUND: This study aimed to determine the prevalence of postpartum metabolic syndrome (MetS), glucose intolerance,
and the determinants, 6-12 weeks postpartum in women with assisted reproduction technology conception
gestational diabetes mellitus diagnosis (ART-GDM) compared to women with spontaneous conception and GDM
diagnosis (SC-GDM).
Materials and Methods: In this prospective cohort study, two groups consisting of 62 ART-GDM and 64 SC-GDM
singleton pregnant women were followed 6-12 weeks after delivery for postpartum MetS. Fasting glucose, 75-g 2-h
OGTT, and lipid profile were assessed. Waist and hip circumference, and systolic and diastolic blood pressures (BP)
were measured at postpartum. Clinical, paraclinical, and obstetric data were recorded from registry offices. The prevalence
of MetS and glucose intolerance were determined. Predictors of MetS and glucose intolerance were evaluated
by logistic regression.
Results: The prevalence of postpartum MetS was 20.8% in ART-GDM women and 10.9% in SC-GDM (P=0.123).
Mean postpartum BMI and systolic BP were significantly higher in the ART-GDM group (P=0.016 and P=0.027
respectively). Adverse pregnancy outcomes were significantly higher in the ART-GDM group. Postpartum glucose
intolerance prevalence did not vary significantly between the groups. Family history of diabetes was a predictive factor
for postpartum MetS and glucose intolerance 6-12 weeks after delivery.
Conclusion: Early postpartum MetS and glucose intolerance prevalence after assisted conception did not vary significantly;
however, postpartum body mass index (BMI) and systolic BP were significantly higher in the ART-GDM group.
Lifestyle modification programs and long-term health care of ART women with GDM diagnosis can be recommended.
Further studies with larger sample size and longer follow-up are necessary to verify our findings.

Gestational diabetes mellitus: Major risk factors and pregnancy-related outcomes: A cohort study.

BACKGROUND: Gestational diabetes mellitus (GDM) is a major pregnancy endocrine problem that has several confirmed risk factors and is associated with adverse pregnancy-related outcomes (PRO). OBJECTIVE: To evaluate the relationship between GDM diagnosis and the associated risk factors of PRO (maternal, intrapartum, perinatal, and neonatal) in accordance with International Association of Diabetes and Pregnancy Study Groups criteria. MATERIALS AND METHODS: This prospective cohort study was performed with 531 singleton parturient (265 GDM and 266 non-GDM). They were selected consecutively from referral hospitals, and the maternal, intrapartum, perinatal, and neonatal outcomes were assessed. RESULTS: The major risk factors influencing the GDM diagnosis were maternal age, obesity, family history of diabetes, previous history of GDM, and previous history of macrosomia. In the comparison of PRO between the groups, significant associations were detected for emergency cesarean delivery, preeclampsia, polyhydramnios, premature rupture of membrane, preterm delivery, and neonatal hyperbilirubinemia in the GDM group. In the multivariate logistic regression analysis, a previous history of stillbirth was significantly associated with maternal and perinatal outcomes. The odds ratios (CI 95%) of the PRO in the women with a GDM diagnosis were: maternal = 2.43 (1.51-3.90), intrapartum = 2.05 (1.35-3.11), perinatal = 2.00 (1.29-3.10), and neonatal = 1.68 (1.08-2.62). The PRO was significantly correlated with GDM diagnosis, but not with the risk factors. CONCLUSION: The adverse pregnancy outcomes were significantly correlated with GDM diagnosis, and the outcomes were not directly affected by the risk factors. Given the related adverse outcomes for mothers and offspring, early screening and management of GDM is necessary especially in Asians and in low-/middle-income countries.

Potential Impact of Diabetes and Obesity on Alveolar Type 2 (AT2)-Lipofibroblast (LIF) Interactions After COVID-19 Infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a new emerging respiratory virus, caused evolving pneumonia outbreak around the world. In SARS-Cov-2 infected patients, diabetes mellitus (DM) and obesity are two metabolic diseases associated with higher severity of SARS-CoV-2 related complications, characterized by acute lung injury requiring assisted ventilation as well as fibrosis development in surviving patients. Different factors are potentially responsible for this exacerbated response to SARS-CoV-2 infection. In patients with DM, base-line increase in inflammation and oxidative stress represent preexisting risk factors for virus-induced damages. Such factors are also likely to be found in obese patients. In addition, it has been proposed that massive injury to the alveolar epithelial type 2 (AT2) cells, which express the SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2), leads to the activation of their stromal niches represented by the Lipofibroblasts (LIF). LIF are instrumental in maintaining the self-renewal of AT2 stem cells. LIF have been proposed to transdifferentiate into Myofibroblast (MYF) following injury to AT2 cells, thereby contributing to fibrosis. We hypothesized that LIF's activity could be impacted by DM or obesity in an age- and gender-dependent manner, rendering them more prone to transition toward the profibrotic MYF status in the context of severe COVID-19 pneumonia. Understanding the cumulative effects of DM and/or obesity in the context of SARS-CoV-2 infection at the cellular level will be crucial for efficient therapeutic solutions.

Knowledge of physicians regarding the management of Type two Diabetes in a primary care setting: the impact of online continuous medical education.

BACKGROUND: To explore the impact of an online continuing medical education (CME) program on physicians' knowledge about the management of type two diabetes. METHODS: An online CME program was designed and uploaded in the CME platform, Department of Education, Ministry of health, Iran. A 28-item questionnaire was used for the assessment. In the beginning, a case scenario was introduced. Then, participants were asked to follow and answer to a pretest assessment. Details of the educational content were provided afterward. Finally, the participants took part in the same post-test exam 4 weeks later. The Wilcoxon matched-pairs signed-ranks test was used to compare the measurements. In addition, the Mann-Whitney test was applied to compare knowledge indices between the general practitioners (GPs) and internists. RESULTS: Five hundred twenty-six primary care physicians participated in this study. There was a significant positive effect regarding diagnosis confirmation (10.3% difference, P = 0.0001). Moreover, a smaller effect was observed in relation to the importance of glycosylated hemoglobin (HbA1c) at diagnosis (5.2% difference, P = 0.0006). The effect was positive in relation to the self-reported HbA1c testing frequency: more than 90% of the participants answered correctly in the post-test exam (7.6% difference, P = 0.0001). Considering improved knowledge in the treatment of diabetes, there was a very significant difference in response to questions targeting advice on a healthy diet, and physical activity; 27.7% (P = 0.000), and 18.7% (P = 0.000), respectively. In addition, the program had a positive impact on various aspects of treatment with oral glucose-lowering drugs (OGLDs). Moreover, the intervention difference was 25, and 34.4% for the questions targeting the appropriate type of insulin, and insulin initiation regimen after OGLD failure. Subgroup analyses revealed that the intervention increased the rate of correct responses among the GPs in various domains of knowledge in diagnosis and treatment. The initial differences between the GPs and internists no longer remained significant after the intervention. CONCLUSION: Knowledge of Iranian primary health care professionals in diabetes management has significant shortcomings. This is concerning because they are at the front line of patient care. We demonstrate the effectiveness of online CME on improving GPs knowledge in the management of type 2 diabetes.

Assisted conception as a potential prognostic factor predicting insulin therapy in pregnancies complicated by gestational diabetes mellitus.

BACKGROUND: Advanced maternal age, family history of diabetes, pre-gestational obesity, increased level of HbA1c, history of gestational diabetes mellitus (GDM), and poor pregnancy consequences are considered risk factors for antenatal insulin requirement in women with GDM. However, the role of assisted reproductive technology (ART) in increasing the risk of insulin therapy in pregnancies complicated with GDM remained elusive. The current study aimed to determine the role of ART in predicting insulin therapy in GDM women and investigate the clinical and biochemical factors predicting the need for insulin therapy in pregnancies complicated with GDM. METHODS: In this prospective cohort study, 236 Iranian women with GDM were diagnosed by one-step oral glucose tolerance test (OGTT) between October 2014 and June 2017. They were mainly assigned to two groups; the first group (n = 100) was designated as ART which was further subdivided into two subgroups as follows: 60 participants who received medical nutrition therapy (MNT) and 40 participants who received MNT plus insulin therapy (MNT-IT). The second group (n = 136) was labeled as the spontaneous conception (SC), consisting of 102 participants receiving MNT and 34 participants receiving MNT in combination with IT (MNT-IT). The demographic, clinical, and biochemical data were compared between groups. Multivariate logistic regression was performed to estimate prognostic factors for insulin therapy. RESULTS: A higher rate of insulin therapy was observed in the ART group as compared with the SC group (40% vs. 25%; P < 0.001). Multivariate logistic regression demonstrated that maternal age ≥ 35 years [OR: 2.91, 95% CI: (1.28-6.62)], high serum FBS [1.10: (1.04-1.16)], HbA1c [1.91 (1.09-3.34)], and ART treatment [2.94: (1.24-6.96)] were independent risk factors for insulin therapy in GDM women. CONCLUSIONS: Apart from risk factors mentioned earlier, ART may be a possible prognostic factor for insulin therapy in pregnancies complicated with GDM.

Stress Hormone and Oxidative Stress Biomarkers Link Obesity and Diabetes with Reduced Fertility Potential.

OBJECTIVE: Tilting the balance in favor of antioxidant agents could increase infertility problems in obese and diabetic individuals. The aim of this study was to evaluate oxidative stress status in semen of men with type 2 diabetes and obesity to investigate whether excessive amounts of oxidative stress, as a result of diabetes and obesity, influence infertility potential. MATERIALS AND METHODS: A case-control study was conducted in men (n=150) attending the Infertility Center of Royan Institute between December 2016 and February 2017. Participants were categorized into four groups; normal weight (BMI<25 kg/m2) and non-type-2 diabetic (control=40), obese and non- type-2 diabetic (obese=40), non-obese and type- 2 diabetic (Nob-DM=35), and obese and type-2 diabetic (Ob-DM=35). The semen analysis was performed according to the World Health Organization criteria. Oxidative stress, DNA fragmentation, sperm apoptosis, and total antioxidant capacity (TAC) were evaluated in semen samples of men. Serum glucose, HbA1c, cortisol, and testosterone levels were determined using the enzyme-linked immunosorbent assay (ELISA) method. RESULTS: Compared with the control group, sperm motility, progressive motility, and normal morphology were significantly decreased in the obese, Nob-DM, and Ob-DM groups (P<0.01). The obese, Nob-DM, and Ob-DM groups showed significantly lower levels of TAC and higher amounts of oxidative stress, early apoptotic sperm, and the percentage of DNA fragmentation as compared with the control group (P<0.05). Testosterone concentration was decreased in the obese, Nob-DM, and Ob-DM groups when compared with healthy individuals (P<0.05), whereas the cortisol level was significantly increased in the Nob-DM and Ob-DM groups in comparison to the obese and control group (P<0.01). CONCLUSION: Increased amount of reactive oxygen species (ROS) levels and DNA fragmentation in men affected by either diabetes or obesity could be considered prognostic factors in sub-fertile patients, alerting physicians to an early screen of male patients to avoid the development of infertility in prone patients.

Reduction of truncated Kit Expression in Men with Abnormal Semen Parameters, Globozoospermia and History of Low or Fertilization Failure.

OBJECTIVE: Phospholipase C zeta 1 (PLCζ) is one of the main sperm factor involved in oocyte activation and other factors may assist this factor to induce successful fertilization. Microinjection of recombinant tr-kit, a truncated form of c-kit receptor, into metaphase II-arrested mouse oocytes initiate egg activation. Considering the potential roles of tr- KIT during spermiogenesis and fertilization, we aimed to assess expression of tr-KIT in sperm of men with normal and abnormal parameters and also in infertile men with previous failed fertilization and globozoospermia. MATERIALS AND METHODS: This experimental study was conducted from September 2015 to July 2016 on 30 normozoospermic and 20 abnormozoospermic samples for experiment one, and also was carried out on 10 globozoospermic men, 10 men with a history low or failed fertilization and 13 fertile men for experiment two. Semen parameters and sperm DNA fragmentation were assessed according to WHO protocol, and TUNEL assay. Sperm tr- KIT was evaluated by flow cytometry, immunostaining and western blot. RESULTS: The results show that tr-KIT mainly was detected in post-acrosomal, equatorial and tail regions. Percentage of tr-KIT-positive spermatozoa in abnormozoospermic men was significantly lower than normozoospermic men. Also significant correlations were observed between sperm tr-KIT with sperm count (r=0.8, P<0.001), motility (r=0.31, P=0.03) and abnormal morphology (r=-0.6, P<0.001). Expression of tr-KIT protein was significantly lower in infertile men with low/ failed fertilization and globozoospermia compared to fertile men. The significant correlation was also observed between tr-KIT protein with fertilization rate (r=-0.46, P=0.04). In addition, significant correlations were observed between sperm DNA fragmentation with fertilization rate (r=-0.56, P=0.019) and tr-KIT protein (r=-0.38, P=0.04). CONCLUSION: tr-KIT may play a direct or indirect role in fertilization. Therefore, to increase our insight regarding the role of tr-KIT in fertilization further research is warranted.

Diagnostic Accuracy of Body Mass Index and Fasting Glucose for The Prediction of Gestational Diabetes Mellitus after Assisted Reproductive Technology.

BACKGROUND: The aim of the present study was to determine the maternal pre-pregnancy body mass index (BMI), first-trimester fasting blood sugar (FBS), and the combination of (BMI+FBS) cut-points for at-risk pregnant women conceived by assisted reproductive technology (ART) to better predict the risk of developing gestational diabetes mellitus (GDM) in infertile women. MATERIALS AND METHODS: In this nested case-control study, 270 singleton pregnant women consisted of 135 (GDM) and 135 (non-GDM) who conceived using ART were assessed. The diagnosis of GDM was confirmed by a one-step glucose tolerance test (O-GTT) using 75 g oral glucose. BMI was classified base on World Health Organization (WHO) criteria. The relationship between BMI, FBS, and BMI+FBS with the risk of GDM development was determined by logistic regression and adjusted for confounding factors. Receiver operating characteristic (ROC) curve analysis was performed to assess the value of BMI, FBS, and BMI+FBS for the prediction of GDM. RESULTS: The GDM group had significantly higher age, BMI, family history of diabetes, and history of polycystic ovary syndrome in comparison with the non-GDM group (P<0.05). Overweight and obese women had 3.27, and 5.14 folds increase in the odds of developing GDM, respectively. There was a 17% increase in the risk of developing GDM with each 1 mg/dl increase in fasting glucose level. The cut points for FBS 84.5 mg/dl (72.9% sensitivity, 74.4% specificity), BMI 25.4 kg/m2 (68.9% sensitivity, 62.8% specificity), and BMI+FBS 111.2 (70.7% sensitivity, 80.6% specificity) was determined. CONCLUSION: The early screening and high-quality prenatal care should be recommended upon the co-occurrence of high FBS (≥84.5 mg/dl) in the first-trimester of the pregnancy and the BMI (≥25.4 kg/m2) in pre-pregnancy period in women undergone ART. The combination of BMI and FBS is considered a better prediction value.

Obstetric and perinatal outcomes of singleton pregnancies conceived via assisted reproductive technology complicated by gestational diabetes mellitus: a prospective cohort study.

BACKGROUND: Growing evidence indicates that the risk of obstetric and perinatal outcomes is higher in women with assisted reproductive technology (ART). However, there is little known about pregnancy related complications and co-morbidity in gestational diabetes mellitus (GDM) following singleton pregnancies achieved by ART in comparison with spontaneous conception (SC). METHODS: Two hundred sixty singleton pregnant women conceived by ART and 314 pregnant women conceived by spontaneous conception (SC) were participated in this prospective cohort study. All participants were enrolled after GDM screening through one-step oral glucose tolerance test (OGTT) and then grouped into GDM and non-GDM groups. Women were followed for pregnancy outcomes including pregnancy-induced hypertension (PIH), preeclampsia, antepartum hemorrhage (APH), cesarean section (CS), preterm birth (PTB), intrauterine growth restriction (IUGR), being small or large for gestational age (SGA or LGA), macrosomia, low birth weight (LBW), respiratory distress, neonatal hypoglycemia, NICU admission and perinatal mortality from antenatal visits to delivery. Confounding factors were adjusted in logistic regression model in order to estimate adjusted odds ratios (aORs). RESULTS: Among 260 ART and 314 SC, 135 and 152 women were GDM women, respectively. Higher maternal age and pre-gravid BMI, shorter duration of gestation and lower gestational weight gain were observed in GDM groups (ART-GDM and SC-GDM) compared to those of the SC group. ART-GDM group had a higher risk (95% confidence interval) of obstetric complications including PIH [aOR:7.04 (2.24-22.15)], preeclampsia [aOR:7.78 (1.62-37.47)], APH [aOR:3.46 (1.28-9.33)], emergency CS [aOR:2.64 (1.43-4.88)], and perinatal outcomes such as PTB [aOR:3.89 (1.51-10.10)], LBW [aOR:3.11 (1.04-9.30)] and NICU admission [aOR:4.36 (1.82-10.45)], as well as neonatal hypoglycemia [aOR: 4.91 (1.50-16.07)], compared to SC group. SC-GDM group showed a higher risk of PIH [aOR: 4.12 (1.31-12.89)], emergency CS [aOR: 2.01 (1.09-3.73] and LGA [aOR: 5.20 (1.07-25.20)], compared to SC group. Additionally, ART group had a higher risk of PIH [aOR: 3.46(1.02-11.68), preeclampsia 5.29 (1.03-27.09), and NICU admission [aOR: 2.53 (1.05-6.09)] compared to SC. Insulin requirement (41.8% vs. 25.7%) was significantly higher in ART-GDM group compared to SC-GDM group. CONCLUSION: The findings of this study suggest that GDM occurring after ART conception increases the risk of adverse obstetric and perinatal outcomes.

Predictive factors of gestational diabetes in pregnancies following assisted reproductive technology: a nested case-control study.

PURPOSE: To evaluate predictive factors for gestational diabetes mellitus (GDM) in singleton pregnancy following assisted reproductive technology (ART). METHODS: This nested case-control study was performed during October 2016-June 2017. Pregnant women who conceived following ART procedures referred to infertility clinic were selected and categorized into GDM and non-GDM based on ADA/IAPDSG criteria. The study variables including age, educational status, first-degree family history of chronic diseases, systolic and diastolic blood pressure, previous obstetric and perinatal outcomes, infertility history, and ART cycle characteristics were collected from medical records. Prediction model to develop GDM was employed by binary logistic regression analysis after adjustment for age and body mass index, family history of diabetes, and gravidity. RESULTS: In total, 270 women with singleton pregnancies (consisted of 135 GDM and 135 non-GDM women) conceived were studied. According to the final model, significant predictors of GDM were history of polycystic ovarian syndrome (PCOS), previous ovarian hyper-stimulation syndrome (OHSS) risk and progesterone injections. Administration of injectable progesterone during the first 10-12 weeks of pregnancy was associated with an approximately twofold increased risk of developing GDM [odds ratio (OR) 2.28, 95% confidence interval (CI) 1.27-4.09)] compared to vaginal progesterone. In addition, the regression analysis revealed that previous OHSS risk (OR 2.40, 95% CI 1.34-4.31) and history of PCOS (OR 2.76, 95% CI 1.26-6.06) were other most important predictors of GDM. CONCLUSIONS: The route of progesterone administration, previous OHSS risk and history of PCOS seem to be putative risk factors for GDM in women conceived by ART.

COMPARE CPM-RMI Trial: Intramyocardial Transplantation of Autologous Bone Marrow-Derived CD133+ Cells and MNCs during CABG in Patients with Recent MI: A Phase II/III, Multicenter, Placebo-Controlled, Randomized, Double-Blind Clinical Trial.

This article published in Cell J (Yakhteh), Vol 20, No 2, Jul-Sep 2018, on pages 267-277, four affiliations (1, 4, 5, and 10) were changed based on authors request.

COMPARE CPM-RMI Trial: Intramyocardial Transplantation of Autologous Bone Marrow-Derived CD133+ Cells and MNCs during CABG in Patients with Recent MI: A Phase II/III, Multicenter, Placebo-Controlled, Randomized, Double-Blind Clinical Trial.

OBJECTIVES: The regenerative potential of bone marrow-derived mononuclear cells (MNCs) and CD133+ stem cells in the heart varies in terms of their pro-angiogenic effects. This phase II/III, multicenter and double-blind trial is designed to compare the functional effects of intramyocardial autologous transplantation of both cell types and placebo in patients with recent myocardial infarction (RMI) post-coronary artery bypass graft. MATERIALS AND METHODS: This was a phase II/III, randomized, double-blind, placebo-controlled trial COMPARE CPM-RMI (CD133, Placebo, MNCs - recent myocardial infarction) conducted in accordance with the Declaration of Helsinki that assessed the safety and efficacy of CD133 and MNCs compared to placebo in patients with RMI. We randomly assigned 77 eligible RMI patients selected from 5 hospitals to receive CD133+ cells, MNC, or a placebo. Patients underwent gated single photon emission computed tomography assessments at 6 and 18 months post-intramyocardial transplantation. We tested the normally distributed efficacy outcomes with a mixed analysis of variance model that used the entire data set of baseline and between-group comparisons as well as within subject (time) and group×time interaction terms. RESULTS: There were no related serious adverse events reported. The intramyocardial transplantation of both cell types increased left ventricular ejection fraction by 9% [95% confidence intervals (CI): 2.14% to 15.78%, P=0.01] and improved decreased systolic wall thickening by -3.7 (95% CI: -7.07 to -0.42, P=0.03). The CD133 group showed significantly decreased non-viable segments by 75% (P=0.001) compared to the placebo and 60% (P=0.01) compared to the MNC group. We observed this improvement at both the 6- and 18-month time points. CONCLUSIONS: Intramyocardial injections of CD133+ cells or MNCs appeared to be safe and efficient with superiority of CD133+ cells for patients with RMI. Although the sample size precluded a definitive statement about clinical outcomes, these results have provided the basis for larger studies to confirm definitive evidence about the efficacy of these cell types (Registration Number: NCT01167751).

Stem cell research and therapy in the Islamic republic of Iran: pioneering in the Islamic world.

In the early 2000s, the Iranian stem cell research and technology had a relatively strong start that benefited from religious blessings, political and public support, as well as scientific endeavors on the part of non-governmental and public research organizations and universities. Later on, it developed a dynamic niche market of public, private start-up, and spin-off companies and organizations that pioneered in the Islamic world in terms of ISI papers, clinical trials, and cell therapy. However, at present, it faces new challenges stemming from the insufficient finance and a comprehensive law and regulation structure to keep its momentum. To remedy this situation, the scientific community and other stakeholders need to have a series of shared long-time goals and try to build consensus on how to achieve them through nationally approved policy documents.

Relationship of leptin administration with production of reactive oxygen species, sperm DNA fragmentation, sperm parameters and hormone profile in the adult rat.

PURPOSE: Leptin, an adipose tissue-derived hormone, plays an important role in energy homeostasis and metabolism, and in the neuroendocrine and reproductive systems. The function of leptin in male reproduction is unclear; however, it is known to affect sex hormones, sperm motility and its parameters. Leptin induces mitochondrial superoxide production in aortic endothelia and may increase oxidative stress and abnormal sperm production in leptin-treated rats. This study aims to evaluate whether exogenous leptin affects sperm parameters, hormone profiles, and the production of reactive oxygen species (ROS) in adult rats. METHODS: A total of 65 Sprague-Dawley rats were divided into three treated groups and a control group. Treated rats received daily intraperitoneal injections of 5, 10 and 30 µg/kg of leptin administered for a duration of 7, 15, and 42 days. Control rats were given 0.1 mL of 0.9 % normal saline for the same period. One day after final drug administration, we evaluated serum specimens for follicle-stimulating hormone (FSH), leutinizing hormone (LH), free testosterone (FT), and total testosterone (TT) levels. Samples from the rat epididymis were also evaluated for sperm parameters and motility characteristics by a Computer-Aided Semen Analysis (CASA) system. Samples were treated with 2',7'-dichlorofluorescein-diacetate (DCFH-DA) and analyzed using flow cytometry and TUNEL to determine the impact of leptin administration on sperm DNA fragmentation. RESULTS: According to CASA, significant differences in all sperm parameters in leptin-treated rats and their age-matched controls were detected, except for TM, ALH and BCF. Serum FSH and LH levels were significantly higher in rats that received 10 and 30 µg/kg of leptin compared to those treated with 5 µg/kg of leptin in the same group and control rats (P < 0.05). ROS and sperm DNA fragmentation was significantly higher in rats injected with 10 and 30 µg/kg of leptin for 7 and 15 days compared with rats treated with 5 µg/kg of leptin and the control group (P < 0.05) for the same time period. However, at day 42 of treatment, ROS and sperm DNA fragmentation levels significantly decreased in all groups (P < 0.05). CONCLUSION: According to these results, leptin can possibly affect male infertility by ROS induction or hormone profile modulation.

Five-year follow-up of the local autologous transplantation of CD133+ enriched bone marrow cells in patients with myocardial infarction.

BACKGROUND: The implantation of a CD133+ bone marrow cell population into an ischemic myocardium has emerged as a promising therapeutic modality for myocardial regeneration and restoration of ventricular contractility. While previous studies have documented the short-term safety and efficacy of CD133+ cell transplantation in patients with acute myocardial infarction, there are few reports of long-term follow-up results. Here, we present the results of long-term follow-up of our acute myocardial infarction patients who were treated with intramyocardial injection of CD133+ cells after coronary bypass graft. METHODS: After five years, 13 patients in the cell transplantation group and 5 patients in the control group underwent safety and efficacy investigations by New York Heart Association classification and two-dimensional echocardiography (2D echo). RESULTS: During the five-year study period, no major cardiac adverse events were reported among patients who received CD133+ stem cells. Regarding efficiency, we observed no statistically significant treatment effects for the echocardiographic parameters [left ventricular end-diastolic and end-systolic volumes, and resting ejection fraction] measured during the follow-up period. However, detailed analysis of regional wall motion revealed an improvement in the Wall Motion Score Index from baseline to the six month follow-up, which was maintained during the follow-up period. CONCLUSION: Taken together, the long-term results of the present study indicate that transplantation of CD133+ is a safe and feasible procedure; however, we could not show any major benefits in our patients. Thus, this issue needs to be addressed by conducting other studies with more patients.

Safety analysis and improved cardiac function following local autologous transplantation of CD133(+) enriched bone marrow cells after myocardial infarction.

The CD133(+) bone marrow cell (BMC) population includes primitive multipotent stem cells which induce neoangiogenesis. Studies suggested transplantation of these cells to infarcted myocardium can have a favorable impact on tissue perfusion and contractile performance. We assessed the feasibility, safety and functional outcomes of autologus CD133(+) BMC transplantation during coronary artery bypass grafting (CABG) in patients with recent myocardial infarction. In a prospective, nonrandomized, open-label study, 27 patients with recent myocardial infarction underwent CABG and intramyocardial injection of autologous bone marrow-derived CD133(+) cells (18 patients, BMC group) or CABG alone (9 patients, control group). At 6 months after CABG, the Wall Motion Score Index (WMSI) was significantly reduced for akinetic/dyskinetic segments treated with CD133(+) cells compared with the control group (P<0.006). Likewise, comparison between baseline and follow up results of dobutamine stress echocardiography and myocardial perfusion scintigraphy showed improvement of myocardial viability and local perfusion of the infarcted zone of the BMC group compared with the control group. No complications related to CD133(+) cell transplantation were noted, either procedurally or during postoperative at a mean of 14 months follow up. In patients with recent myocardial infarction, transplantation of CD133(+) cells to the peri-infarct zone during CABG surgery is feasible and safe, with no evidence of early or late adverse events. Moreover, these cells might restore tissue viability and improve perfusion of the infarcted myocardium, suggesting that they may induce myogenesis as well as angiogenesis.

A study of malnutrition in Iranian patients with primary antibody deficiency.

Nutrition is an important factor that influences immunity, and nutritional deficiencies can impair resistance to infections. Malnutrition is the most common cause of immunodeficiency worldwide. Trace elements such as zinc, selenium, iron, and copper can influence several components of immunity. Primary antibody deficiency disorders are a group of disorders characterized by an unusual susceptibility to infections and malnutrition. Impaired nutritional status has been reported in immunodeficient patients. The aim of this study was to determine anthropometric indices and trace elements status in these patients. Thirty-eight children (28 males, 10 females, aged 2-18 years) with primary antibody deficiency referring to Children's Medical Center of Tehran University of Medical Science were enrolled in this research. Primary immunodeficiency disorders consisting of CVID, XLA, IgA deficiency, IgG subclass deficiency, and hyper IgM were assessed. Anthropometric indices, comprised of height, weight that were measured and body mass index (BMI) was calculated. Height-for-age (HAZ), weight-for-height (WHZ) and weight-for-age (WAZ) were determined according to Z-score to study mild, moderate and severe malnutrition. Serum copper, zinc, selenium and iron levels were measured by an atomic absorption spectrometer. The most common disorders were CVID 52.5% and X-linked agammaglobulinaemia 27.5%. Based on BMI measurements 21.1% of patients had malnutrition. According to HAZ, 13.2%, 13.2% and 36.8% had severe, moderate and mild malnutrition, respectively. According to WAZ, 10.5%, 18.4% and 28.6% had severe, moderate and mild malnutrition, respectively. Regarding to WHZ, 14.3% and 28.6% had moderate and mild malnutrition, respectively. Low selenium levels and high copper levels were observed in 37.5% and 70.3%, respectively. Anthropometric data showed that the frequency of malnutrition in these patients was higher than the CDC standard. Low serum selenium levels and high serum copper levels were observed, suggesting further research is needed on these parameters. Most of the patients had serum zinc and iron levels within the normal range. It is recommeded that clinical immunologists and nutritionists should make a collective effort to provide these patients with standard or specialized diets so as to decrease the risk of infection.