مجله دانشکده پزشکی دانشگاه علوم پزشکی تهران
سال هفتاد و سوم شماره 11 (پیاپی 179، بهمن 1394)

Angiogenesis, as the process of new vessel formation from pre-existing vessels is dependent on a delicate equilibrium between endogenous angiogenic and antiangiogenic factors. However, under pathological conditions, this tight regulation becomes lost which can result in the formation of the different diseases such as cancer. Angiogenesis is a complex process that includes many gene products that are produced by different cells. Each of the processes influenced by specific genes that their expression can be regulated by hypoxi inducible factor-1 (HIF-1). Hypoxia, the imbalance between the oxygen in need and the oxygen available, usually occurs in tumors and ischemic cardiovascular diseases. In order to overcome this challenge, tumors regulate and control the expression of genes related to angiogenesis, cell cycle and metabolism using hypoxia-inducible factor 1 (HIF-1). HIF-1 was first recognized as a transcription factor involved in hypoxia-induced erythropoietin expression. As angiogenesis pathway molecules are being described, this factor has been characterized as a key transcription regulator for these molecules. In this review article, after discussing HIF-1 structure and characterization, the role of this important factor in angiogenesis and cancer as a pathological case and finally, the clinical applications has been evaluated. Articles related to the key words of hypoxia, HIF-1 and angiogenesis were searched from valid databases such as Springer Link, google scholar, Pubmed and Sciencedirect. Then, the articles related to the role of hypoxia and HIF-1 in activation of genes that are involved in angiogenesis and cancer were searched and selected for this study. Studies show that, HIF-1 activation of genes including vascular endothelial growth factor (VEGF), angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2), etc., induced angiogenesis in the tumor cells. Furthermore, the activation of genes such as insulin-like growth factor 2 (IGF2), transforming growth factor α (TGF-α) and MAPK and PI3K signaling pathway will also enable the survival and proliferation of tumor cells. HIF-1 by activating genes involved in angiogenesis and also activates signaling pathways associated with cell survival and proliferation plays an important role in the stability and growth of tumors. Therefore, better understanding of molecular mechanisms associated with this factor can be effective in the treatment of cancer.

Graft survival has been considered the major problem in reconstructive surgery. Clinical studies have helped us to understand the role of PRP in increasing skin survival. Our goal in this study was to examine the treatment effects of platelet-rich plasma (PRP) and platelet-rich fibrin (PRF) on autologous full thickness skin graft survival in male rats.
This experimental study was performed on 36 rats of Sprague-Dawley race with weighing approximately 250 to 300 gr on May 2015 in animal laboratory of Hazrat Fatima Hospital. After anesthesia, rats were divided into 3 groups. We injected platelet-rich plasma (PRP) in the first group, platelet-rich fibrin (PRF) in the second and saline in the third group after removing the skin. Microscopic analysis was performed with camera (Canon powershot SX200, Tokyo, Japan) on days 7, 14, 21 and 28 after surgery. We used image analysis system (ImageJ, ver. 1.45) to examine necrosis and survival rate. Samples were studied with H&E staining on day 28 microscopically for histological analysis of vascular density and angiogenesis.
Our findings showed the area of necrosis in animals injected with PRP on days 7 and 14, was meaningfully less than control group (P= 0.0001). There was no meaningful difference between control and PRP groups (P> 0.05). The area of necrosis in animals injected with PRF did not have any significant difference with control group from beginning to 21st day (P According to our results in this study, we can conclude that using autologous PRP can enhance the process of healing soft tissue injury and be affective at increasing graft survival. This method is suggested to be conducted for patients highly at risk of graft loss and also for those who are in need of early treatments.

Staphylococcus aureus is a gram positive coccus which is able to cause different kinds of infection in certain condition. The function of this bacteria is to provide the conditions for the invasion of it to the host with the secretion of different sorts of toxins such as Staphylococcus aureus enterotoxin, including important virulence factors that super antigens are all factors digestive inconvenience. Staphylococcus aureus enterotoxin-secreting toxins such conditions provides invasion of host genes. There are different types of SE, but type A enterotoxin (SEA) and type B enterotoxin (SEB) are the most important types. Therefore, in this study, the prevalence of Staphylococcus aureus toxin-producing enterotoxin genes (SEB, SEA) in clinical strains isolated from patients in teaching hospitals of Shahrekord city, Iran, were studied.
This cross-sectional and descriptive study, which was conducted from May 2014 to December 2014. A hundred and ten isolates of Staphylococcus aureus from patients collected over a period of 8 months and were first identified using standard biochemical methods and laboratory. Using standard methods and laboratory tests were identified and compared with the antibiotic oxacillin minimum inhibitory concentration were determined by broth micro dilution, and then they were assessed by polymerase chain reaction (PCR) technique.
The results indicated that, 110 samples of dairy products infected by Staphylococcus aureus were detected. Two cases (1.8%) of these infected samples were carrying both enterotoxin A and enterotoxin B genes. The frequencies of enterotoxin A genes were twenty-six cases (23/6%) and The frequencies of enterotoxin B genes were two cases (1/8%), respectively.
The detection of enterotoxin A and enterotoxin B genes, shows the most important role they have in bringing about superinfection. The detection of enterotoxin A and B genes, shows the most important role they have in bringing about superinfection. Enterotoxins SEA and SEB are heat stable; therefore heating has no effect on dairy products contaminated by enterotoxins and gastritis may occur in a short period of time. As PCR is a rapid, sensitive, specific and inexpensive method, we suggest that it can be replaced to traditionally assays for detecting Staphylococcus aureus enterotoxin.

Author(s): Bloodstream infections (BSI) have a high incidence and high mortality in the worldwide. The mortality rate is variable between 20-70%. Therefore, early and timely detection of BSI agent in clinical laboratories is necessary. The aim of this study was to determine an efficient diagnostic tool to septicemia in accompany of blood culture method by Real-time PCR (using panbacterial 23S rRNA gene).
This cross-sectional study was conducted in two analytical and clinical stages in Hamadan University of Medical Sciences, Iran, from October 2014 to June 2015. In analytical stage, sensitivity (by serial dilution from 104 to 1 CFU/ml) and specificity of the primer were evaluated with the Staphylococcus aureus (as Gram positive indicator bacteria) and Escherichia coli (as Gram-negative indicator bacteria), human genome (from Hella cell culture), Candida albicans yeast and Aspergillus fumigatus fungus. In clinical stage, 121 blood samples were collected from patients suspected to sepsis in intensive care unit (ICU) from Hamadan University Hospitals. Finally, the results of Real-time PCR and blood culture methods were compared.
The Real-time PCR showed a sensitivity ranging from 2 to 10 target copies per reaction to the whole blood for Escherichia coli and Staphylococcus aureus respectively. The specificity of this method was evaluated and no false positive amplification was identified. 57.85% (70 cases) of the samples were positive by Real-time PCR and 13.22% (16 cases) of the samples were positive by blood culture. However, none of the cases that were positive by blood culture were negative in Real-time PCR. As well as, 44.62% (54 cases) of cases were positive by Real-time PCR but blood culture showed no bacteria in the samples, and 42.15% (51 cases) were negative by both methods. Correlation or agreement of Kappa was 0.20, that indicating poor agreement between the two methods.
Real-time PCR is more sensitive than blood culture and also, because of high sensitivity of this primer by Real-time PCR, we can use it for screening blood samples from suspected patients of sepsis.

Recently, the role of inflammation and oxidative stress in the pathophysiology of atrial fibrillation (AF) after cardiac surgery has been emphasized. Vitamin C as an antioxidant important role in reducing the incidence of postoperative atrial fibrillation. This study aimed to investigate, administration of vitamin C, as a way to reduce the incidence of atrial fibrillation after coronary bypass surgery.
In this double-blind clinical study, 290 patients in Rajaee Heart Center, from March 2013 to December 2014 who underwent coronary artery bypass surgery were randomly divided into intervention and control groups to receive vitamin C and placebo. The intervention group before the surgery in the operating room received 2 grams of vitamin C intravenously then one gram per day for four days prior to surgery. After the operation, the two groups were compared in terms of the following: Atrial and ventricular arrhythmias after surgery, ICU stay and hospital stay and duration of intubation.
113 cases and 177 controls (191 men and 99 women) with a mean age of 55.40±14.40 years in both groups (vitamin C and placebo) were enrolled. The incidence of postoperative atrial fibrillation was 55% in the placebo group to 35% in the vitamin C group decreased (P= 0.001). Duration of intubation in the intervention group 11.8 and the control group was 14.14 hours (P= 0.004). The amount of drainage was lower in vitamin C group (P= 0.003). Vitamin C had no effect on the rates of hospital and ICU stay (P= 0.075). There was no significant reduction in threatening arrhythmia (VT) and VF in this period (P= 0.159).
Vitamin C supplements may reduce atrial fibrillation after coronary artery bypass surgery also can improve conditions such as reducing the duration of intubation. With regard to the safety, these supplements can be recommended for the prevention of atrial fibrillation before coronary artery bypass surgery.

Sexual dysfunction could be under the influence of some underlying medical problems. The purpose of this study is to examine the relationship between medical problems and sexual function in post-menopausal women.
This is a community-based, descriptive-correlation study of 405 post-menopausal women residing in Chalus and Nowshahr cities, North of Iran, aged 40 to 65 years old from October 2013 to May 2014. A multistage, randomized sampling was conducted. The data was acquired through interviews using the Female Sexual Function Index (FSFI) questionnaire and a researcher-made questionnaire, and was analyzed using descriptive and analytical tests such as multiple linear regression and logistic regression models.
51.4% of the subjects had medical conditions. Cardiovascular disorders were the most common diseases among the subjects. 61% of the women were suffering from female sexual dysfunction (FSD). Sexual dysfunction in patients with medical conditions was significantly higher (P= 0.037). Scores of arousal (P= 0.000), orgasm (P= 0.018), and satisfaction (P= 0.026), as well as the FSFI total score (P= 0.005), were significantly lower in subjects with cardiovascular disorders. Scores of desire (P= 0.001), arousal (P= 0.006), lubrication (P= 0.010), orgasm (P= 0.004), and satisfaction (P= 0.022), as well as the FSFI total score (P= 0.017), were significantly lower in subjects with diabetes. Scores of pain were significantly lower in subjects with musculoskeletal disorders (P= 0.041), they experienced more pain during intercourse. In domains of arousal (P= 0.030), satisfaction (P= 0.040), and pain (P= 0.044), the scores of those taking antihypertensive medications were significantly lower than the scores of the rest of the subjects. Scores of desire (P= 0.001), arousal (P= 0.006), orgasm (P= 0.006), and satisfaction (P= 0.048), as well as the FSFI total score (P= 0.006), were significantly lower in those taking antidiabetic drugs. And lastly, the mean satisfaction score in women whose spouse had medical conditions was significantly lower (P= 0.040).
Cardiovascular disorders, diabetes, and musculoskeletal disorders could have a negative impact on sexual function in post-menopausal women. Thus, these diseases must be considered and treated in order to improve women’s health, particularly their sexual function.

Pain control after orthognathic surgeries due to severity of pain and limitations of opioids use in these patients are particular importance. The aim of this study was to evaluate the effect of oral gabapentin and intramuscular ketorolac in combination with intravenous acetaminophen for pain control after this surgery.
This study was a randomized clinical trial (RCT) on 75 patients (18-60 years old American Society of Anesthesiologists (ASA) physical status classification system, I, II) that undergo orthognathic surgery in Sina University Hospital, Tehran University of Medical Sciences, Tehran, Iran from June 2013 to August 2014. The patients were randomly divided in 3 groups. All of groups received 1 gr (intravenous acetaminophen) 30 minutes before the end of surgery. The control group (n= 25) received placebo. The second group (n= 25) received 30 mg ketorolac intramuscular after induction of anesthesia and the third group (n= 25) received 600 mg Gabapentin orally 30 minute before the induction of anesthesia. The pain severity score assessed by visual analogue scale (VAS), the level of sedation assessed by Ramsey scale, opioid requirement, nausea and vomiting was recorded in the post-anesthesia care unit (PACU) at 1, 3, 6, 12 and 24 hours after surgery. For rescue pain management intravenous morphine was administered.
Seventy-five patients were enrolled in this study. Use of Ketorolac and gabapentin declines the pain intensity, level of agitation and morphine requirement in the recovery room and early hours in the ward (P= 0.011). The 24-hour opioid consumption, nausea and vomiting was significantly higher in control group compared with the both intervention groups (15±1.4 vs. 5±0.5 mg) (P The result of this study suggest that ketorolac as well as gabapentin can decline the pain intensity and opioid requirement with less nausea and vomiting and good hemodynamic control after orthognathic surgery.

Over the last two decades invasive candidiasis has become an increasing problem in neonatal intensive care units (NICUs). Colonization of skin and mucous membranes with Candida spp. is important factor in the pathogenesis of neonatal infection and several colonized sites are major risk factors evoking higher frequencies of progression to invasive candidiasis. The aim of this study was to detect Candida colonization in NICU patients.
This cross-sectional study was conducted on 93 neonates in NICUs at Imam Khomeini and Children Medical Center Hospitals in Tehran. Cutaneous and mucous membrane samples obtained at first, third, and seventh days of patients’ stay in NICUs during nine months from August 2013 to May 2014. The samples were primarily cultured on CHROMagar Candida medium. The cultured media were incubated at 35°C for 48h and evaluated based on colony color produced on CHROMagar Candida. In addition, isolated colonies were cultured on Corn Meal Agar medium supplemented with tween 80 for identification of Candida spp. based on their morphology. Finally, polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was performed for definite identification of isolated species.
Colonization by Candida spp. was occurred in 20.43% of neonates. Fifteen and four patients colonized with one and two different Candida spp., respectively. Isolated Candida spp. identified as; C. parapsilosis (n: 10), C. albicans (n: 7), C. tropicalis (n: 3), C. guilliermondii (n: 2), and C. krusei (n: 1). In present study non-albicans Candia species were dominant (69.56%) and C. parapsilosis was the most frequent isolate (43.47%). Using Fisher's exact test, the correlation between fungal colonization with low birth weight, low gestational age, and duration of hospital stay was found to be statistically significant (P=0.003).
The results of this study imply to the candida species colonization of neonates. Neonates in NICU are at the highest risk for severe infection with Candida parapsilosis. Therefore, isolation of C. parapsilosis as the most common species (43.47%) in present study was noteworthy.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorders in reproductive age women. These women confer with complications of pregnancy such as gestational diabetes, pregnancy-induced hypertension, preeclampsia and neonatal complications such as small for gestational diabetes (SGA) are more prevalence in women with PCOS. The aim of this study was to evaluate the incidence of complications associated with PCOS in pregnant women.
This was an observational and prospective study which recruited 205 pregnant women with PCOS from Imam Khomeini Hospital, Ahvaz Jundishapur University of Medical Sciences (AJUMS) between 2013 and 2014. Inclusion criteria were women with PCOS and gestational age over 20 weeks. The demographic and clinical variables including mother's age, body mass index (BMI) and conditions of pregnancy including pregnancy-induced hypertension, preeclampsia, gestational diabetes and overt diabetes and neonatal complications such as preterm labor (PTL), SGA and intrauterine fetal death (IUFD) were recorded.
The prevalence of hypertension disorders, preeclampsia, gestational diabetes and overt diabetes were observed in 44 (21.5%), 18 (8.8%), 29 (14%) and 22 (11%) patients, respectively. The history of familial diabetes was shown in 28 patients (13.6%). In addition, the history of pregnancy induced hypertension was reported in 25 patients (12.1%). Only 6 patients (2.9%) had history of gestational diabetes. Among neonatal complications due to PCOS, SGA with 15.3% and then PTL with 12.6% had highest prevalence. IUFD was shown only in 2 patients.
Pregnant women with PCOS are at the higher risk for pregnancy and neonatal complications. Specifically, these women should be evaluated for pregnancy induced hypertension during pregnancy than others.