A Single-group, Clinical Interventional Study on the Effect of Iron Deficiency Anemia on Blood Glucose and Insulin Resistance in Women with Type II Diabetes.

AIMS: Iron deficiency anemia (IDA) is one of the disorders recently associated with an increase in insulin resistance (IR) and, consequently, diabetes mellitus (DM) affection by causing oxidative stress. In this study, we look at how IDA may contribute to developing type II diabetes mellitus (T2DM), controlling diabetes, and reducing IR in women with T2DM. METHODS: In this single group, clinical interventional study, we enrolled 40 women with T2DM and IDA. Before and after intervention with ferrous sulfate tablets, their blood glucose (BG) levels and IR levels were evaluated. This study was approved by the Ethics Committee of Qom University of Medical Sciences (ethics code: IR.MUQ.REC.1397.031) and registered at the Iranian Center for Clinical Trials (No. IRCT20170215032587N3). A significant level was considered p <0.05. RESULT: The mean age of patients was 48.18 ± 4.6 years, with 5.3-5.8 years duration of T2DM. After the intervention, the mean fasting blood glucose (FBG) level reached 198.53 ± 48.11 to 170.93 ± 37.41, which was significant (p <0.0001). Also, hemoglobin A1C level reached from 8.49 ± 0.9 to 7.96 ± 0.58, which was significant (p <0.0001). Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) demonstrating a significant reduction of IR levels after intervention with ferrous sulfate tablets (p <0.018). CONCLUSIONS: IDA treatment in patients with T2DM can significantly reduce the BG and IR levels. To better control BG, checking iron status and its correction may provide better clinical outcomes in these patients. CLINICAL TRIAL REGISTRATION NUMBER: IRCT20170215032587N3.

Comparison of the Efficacy of Oral Magnesium with Oral Ketorolac for Postoperative Pain Management in Anorectal Surgery: A Double-blinded Randomized Clinical Trial.

BACKGROUND: Due to the presence of postoperative pain in patients undergoing anorectal surgery, and since the pain affects the quality of life of patients, we aimed to compare the analgesic effectiveness of oral magnesium with oral ketorolac to choose the right analgesic drug for these patients. METHODS: This study was a double-blind, randomized clinical trial performed on 104 candidates undergoing anorectal surgery. Patients were randomly divided into two groups. Group 1 received oral magnesium (250 mg daily), and group 2 received oral ketorolac (10 mg daily). The medicine was given to the patient 2 hours after the operation and every 12 hours for 10 days. Pain measurements were recorded at 24-hour intervals after surgery based on the visual analog scale and numerical rating scale. RESULTS: This study found that postoperative pain was reduced in patients taking magnesium tablets, similar to the ketorolac group. A similar decreasing trend was observed in the group receiving ketorolac; however, the reduction was more pronounced in the magnesium group and was statistically significant on days 1, 3, and 5 (p < 0.001). However, insignificant differences were noted between the two groups on the seventh (p = 0.093) and tenth (p = 0.088) postoperative days. CONCLUSION: Taking magnesium tablets after surgery has a suitable analgesic effect, which is similar to oral ketorolac tablets from the fifth day onwards, but in the initial days, it is less effective than ketorolac statistically.

Choosing the Right Protocol to Establish MCF-7 Tumor Xenograft in Nude Mice.

BACKGROUND: Xenografts of various human cancers in nude mice provide a helpful model in cancer research. This study aimed to develop a xenograft mouse model of MCF-7 breast cancer using injectable estradiol valerate. METHODS: Thirty healthy female C57 nu/nu mice were engrafted with three protocols to establish an MCF-7 tumor. Injectable estradiol valerate (10 mg/ml) was used as a substitute for estradiol pellets. The development of tumors was recorded daily, and data were statistically analyzed. Histology of bladder, kidney, and tumors was used to estimate tumor establishment and probable urinary adverse effects. RESULTS: According to the findings, the duration of MCF-7 tumor growth was the lowest for protocol B (tumor tissue). Also, this protocol had the highest xenograft yield within the shortest time duration (37 days for protocol B vs. 73 days for protocol A) without causing urinary adverse effects. CONCLUSION: Our findings revealed that estradiol valerate, which is way less expensive than estradiol pellets, can be used as a tumor proliferator to establish MCF-7 tumors with the highest yield when MCF-7 tumors have been used for xenograft.

Various Aspects of Fasting on the Biodistribution of Radiopharmaceuticals.

It is demonstrated that fasting can alter the biodistribution of radiopharmaceuticals in nuclear medicine. Various studies have highlighted that fasting is interpreted to be easy for physicians during PET study, fasting is one of the most important factors determining the usefulness of this protocol. It is well documented that fasting can suppress normal 18F-FDG PET uptake during nuclear cardiology. However, there is no consensus about the usefulness of fasting on radiopharmaceuticals, especially on 18F-FDG in PET imaging, but special attention should be paid to the setting of the fasting duration. Nevertheless, it does seem we still need extensive clinical studies in the future. The present study aims to review the various aspects of fasting, especially metabolic alteration on radiopharmaceutical biodistribution. In this study, we focused more on the effect of fasting on 18F-FDG biodistribution, which alters its imaging contrast in cardiology and cancer imaging. Therefore, shifting substrate metabolism from glucose to free fatty acids during fasting can be an alternative approach to suppress physiological myocardial uptake.

The effects of Sorafenib and Natural killer cell co-injection in combinational treatment of hepatocellular carcinoma; an in vivo approach.

BACKGROUND: Natural killer cells (NKC) and Sorafenib (Sor) are two important agents for the treatment of hepatocellular carcinoma (HCC). Over the past decade, the interaction of Sor and NKC against HCC has been widely challenging. This study aimed to assess the efficacy of NKC & Sor for the treatment of HCC in vivo. METHODS: Subcutaneous xenograft models of HCC were established in nude mice. For safety assessment of treatment, the kidney and liver functions were analyzed. Paraffin embedded tumor sections were histopathologically studied and immunohistochemistry (IHC) tests were done to evaluate the angiogenesis (CD34) and proliferation (Ki67) indexes. The terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was performed to identify the tumor cells undergoing apoptosis. The serum levels of tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) were measured by enzyme-linked immunosorbent assay (ELISA) and expression levels of major inflammatory cytokines and cytoplasmic granules in xenograft HCC were quantified using real-time PCR. RESULTS: NKC & Sor significantly inhibited necrosis and apoptosis in tumor cells and increased angiogenesis and proliferation of HCC compared to the monotherapy of NKC or Sor alone. The serum levels of TNF-α, IFN-γ as well as the expression levels of TNF-α, IFN-γ, interleukins (ILs)-1, 6, 10, granzyme-B and perforin in the xenograft HCC tissues of the treated mice with NKC & Sor were significantly lower than those of treated with NKC or Sor alone. CONCLUSION: Therapy with the specific dosage of NKC & Sor could not inhibit the HCC xenograft growth rate through a synergistic effect in a mouse model of HCC.

Uncommon cause of respiratory failure due to a bezoar in the hypopharynx: a case report.

BACKGROUND: Trichotillomania and trichophagia cause trichobezoars, which are masses made of hair. The main presentation of this condition is abdominal pain. However, other complications include gastric outlet obstruction, nausea, vomiting, weight loss, malnutrition, hematemesis, diarrhea, and constipation. CASE PRESENTATION: A 57-year-old woman with trichotillomania was admitted to the Emergency Department with the chief complaints of dyspnea on exertion, shortness of breath, dysphagia, generalized weakness, and hoarseness. Spiral chest computed tomography (CT) scan did not reveal any parenchymal lesions Pulmonary CT angiography did not reveal pulmonary embolism. The patient was admitted to the Surgery Department for hand fasciotomy due to contrast leakage, and during laryngoscopy, a trichobezoar was detected that was removed with Magill forceps. CONCLUSIONS: Rare cases of trichobezoars can be observed in humans with gastrointestinal and respiratory symptoms. Precise and timely diagnosis are key for the prevention of more invasive diagnostic procedures.

Comparing the Efficacy and Safety of Dexmedetomidine/Ketamine with Propofol/Fentanyl for Sedation in Colonoscopy Patients: A Doubleblinded Randomized Clinical Trial.

BACKGROUND: In this double-blinded randomized clinical trial, we aimed to compare the safety and efficacy of a combination of Dexmedetomidine and Ketamine (DK) with Propofol and Fentanyl (PF) for sedation in colonoscopy patients. METHODS: In this study, 64 patients who underwent colonoscopy were randomized into two groups: 1) A, which received PF, and 2) B, which received DK for sedation. Among 64 patients, 31 patients were included in PF, and 33 patients were included in the DK group. Both groups were similar in terms of demographics. Patients' sedation score (based on Ramsay sedation scale) and vital signs were recorded at 2, 5, 10, and 15 minutes. Complications including apnea, hypotension, hypoxia, nausea, and vomiting, along with gastroenterologist satisfaction and patients' pain score (based on Wong-Baker faces pain assessment scale), were recorded by a checklist. Data were analyzed by SPSS v.18 software, using chi-square, independent t-tests, and repeated measures analysis with p<0.05 as the criterion for significant differences. RESULTS: The mean score of sedation was 4.82±0.49 in the DK group and 5.22±0.45 in the PF group (p value=0.001). Serious complications, including hypotension (p value=0.005) and apnea (p value=0.10) were significantly higher in the PF group. Satisfaction of gastroenterologist (p value= 0.400) and patients' pain score (p value = 0.900) were similar among groups. CONCLUSION: Combination of DK provides sufficient sedation with fewer complications in comparison with PF in colonoscopy patients.

Inflammatory Bowel Disease Management during the COVID-19 Pandemic: A Literature Review.

BACKGROUND: Coronavirus disease 2019 (COVID-19) caused a global pandemic. Since its start, widespread safety measures have been adopted by nations worldwide. Crohn's disease (CD) and ulcerative colitis are two forms of inflammatory bowel disease (IBD). IBD is a common inflammatory illness with a high worldwide incidence. Its clinical symptoms include stomach discomfort, diarrhea, anorexia, and weight loss. Genetics, microbes, cigarette smoking, appendectomy, lack of personal hygiene, using anti-inflammatory agents, vitamin D deficiency, and stress are the main risk factors for IBD. COVID-19 pandemic raised concerns about the exacerbation of COVID clinical manifestations in patients with IBD and increasing the risk of mortality. During COVID-19 pandemic, intestinal inflammation, and promoting adherence need to be controlled using medications and vaccinations as a primary goal. In this review, we reviewed unique concerns about IBD risk in the population as well as management of the disease, and the effectiveness of vaccination during COVID-19 pandemic.

Gastrointestinal and Pancratohepatobiliary Cancers: A Comprehensive Review on Epidemiology and Risk Factors Worldwide.

A significant number of cancer cases are afflicted by gastrointestinal cancers annually. Lifestyle and nutrition have a huge effect on gastrointestinal function, and unhealthy habits have become quite widespread in recent decades, culminating in the rapid growth of gastrointestinal cancers. The most prevalent cancers are lip and mouth cancer, esophageal cancer, gastric cancer, liver and bile duct cancer, pancreatic cancer, and colorectal cancer. Risk factors such as red meat consumption, alcohol consumption, tea, rice, viruses such as Helicobacter pylori and Ebstein Bar Virus (EBV), along with reduced physical activity, predispose the gastrointestinal tract to damage and cause cancer. According to the rapid increase of cancer incidence and late diagnosis of gastrointestinal malignancies, further epidemiological researches remain necessary in order to make appropriate population-based preventive policies. In this study, we reviewed clinical symptoms, risk factors, preventative measures, as well as incidence and mortality rates of gastrointestinal malignancies worldwide with focus on Iranian population.

Synthesis of New Thioureas Derivatives and Evaluation of Their Efficacy as Proliferation Inhibitors in MCF-7 Breast Cancer Cells by Using 99mTc-MIBI Radiotracer.

BACKGROUND AND OBJECTIVES: Anti-tumor activity of some thioureas derivatives is well documented in literature and received considerable attention. The present study aims to synthesize and characterize some novel thioureas and carbonylthioureas as anti-tumor agents for MCF-7 breast cancer cells in vitro and in vivo. MATERIALS AND METHODS: Several 1-allyl-3-(substituted phenyl), N,N'-(phenylene) bis(3- allyldithithiourea) and 1-cyclopropanecarbonyl-3-(substituted phenyl)-thioureas derivatives were synthesized and confirmed by FT-IR spectroscopy, NMR and 13C-NMR. Anti-tumor activity of these compounds was determined by various in vitro and in vivo assays including; MTT, tumor volume measurement as well as,99mTc-MIBI tumor uptake in MCF-7 tumor bearing nude mice. RESULTS: Among all of the synthesized compounds, some thioureas derivatives [3i] and [4b] at 100 nM concentration exhibited significant inhibitory effects on the proliferation of MCF-7 cell in vitro. However, this inhibition was not observed in HUVEC human endothelial normal cells. In vivo anti-tumor effects of the synthesized compounds on MCF-7 xenograft mouse models demonstrated a reduction in the tumor volume for various concentrations between 2 to 10 mg/kg after 21 days. These effects were comparable with Tamoxifen as standard anti-estrogen drug. According to the 99mTc-MIBI biodistribution result, treatment of MCF-7 bearing nude mice with both [3i] and [4b] compounds at the maximum concentration (10 mg/kg) can lead to a significant decrease of 99mTc- MIBI tumor uptake. CONCLUSION: Compounds [3i] and [4b] suppressed the growth of MCF-7 cells in the xenograft nude mice at the doses that were well-tolerated. Our study suggests that these new compounds with their significant anti-tumor effects, may serve as useful candidates for breast cancer therapy.

Evaluation of Anti-Tumor Potential of Lactobacillus acidophilus ATCC4356 Culture Supernatants in MCF-7 Breast Cancer.

BACKGROUND: The anti-cancer activity of some lactic acid bacterial strains is well documented in several kinds of literatures. Lactobacillus strains have received considerable attention as a beneficial microbiota. The aim of this study is to evaluate the effects of anti-tumor activities of L. acidophilus ATCC4356 culture supernatants on the MCF-7 human breast cancer cells. MATERIALS AND METHODS: The anti-cancer effects of 24h and 48h culture supernatants at various concentrations (1.25, 2.5, 5, 10 and 20 µg/ml) were determined by various in vitro and in vivo assays including MTT, tumor volume measurement as well as 99mTc-MIBI biodistribution in MCF-7 tumor bearing nude mice and histopathology test. For evaluation of the related mechanism of action, quantitative PCR was conducted. RESULTS: The 48h culture supernatants at 10 and 20 µg/ml exhibited significant in vitro inhibition of MCF-7 cell proliferation. However, this inhibition was not observed for HUVEC human endothelial normal cells. Q-PCR indicated that treatment by the supernatant led to a significant downregulation of VEGFR (~ 0.009 fold) and Bcl- 2 (~ 0.5 fold) and upregulation of p53 (~ 1.3 fold). In vivo study using MCF-7 xenograft mouse models demonstrated a reduction in tumor weight and volume by both 24h and 48h supernatants (2 mg/kg) after 15 days. According to the 99mTc-MIBI biodistribution result, treatment of MCF-7 bearing nude mice with both 24h and 48h supernatant (2mg/kg) led to a significant decrease in tumor uptake compared with the control group. CONCLUSION: These results suggest that the culture supernatants of L. acidophilus ATCC4356 at suitable concentrations can be considered as a good alternative nutraceutical with promising therapeutic indexes for breast cancer.

Adding ursodeoxycholic acid to the endoscopic treatment and common bile duct stenting for large and multiple biliary stones: Will it improve the outcomes?

BACKGROUND: The role of common bile duct (CBD) stenting in the establishment of bile stream in the elderly patients and the ones who are not good candidates for surgery due to not responding to treatments was well documented in previous studies. The current study aimed at investigating the effect of adding Ursodeoxycholic acid (UDCA) to CBD stenting alone in order to reduce the size of large and multiple CBD stones. METHODS: Clinical outcomes including success rates in CBD stones clearance, incidence of pancreatitis, perforation, bleeding, as well as, decrease in size of stones and liver enzymes after a two-month period were assessed in the UDCA + CBD stenting group. RESULTS: A total of 64 patients referring to Shahid Beheshti Hospital in Qom, Iran with multiple or large CBD stones (above three or larger than 15 mm) received standard endoscopic therapies and UDCA + CBD stenting (group B) and controls only received standard endoscopic therapies with only CBD stenting (group A). The mean reduction in the size of stones in group B was significantly higher than that of group A (3.22 ± 1.31 vs 4.09 ± 1.87 mm) (p = 0.034). There was no difference in the incidence rate of complications including pancreatitis, cholangitis, bleeding, and perforation between the two groups (P > 0.05). CONCLUSION: Adding UDCA to CBD stenting, due to decrease in the stone size and subsequently facilitation of the stones outlet, can be considered as the first-line treatment for patients with large and multiple CBD stones. Also, in the cases with large or multi stones may be effective in reducing size and subsequently stone retrieval. Trial registry The study protocol was approved by the Ethics Committee of Qom University of Medical Sciences (ethical code: IR.MUQ.REC.1397.075); the study was also registered in the Iranian Registry of Clinical Trials (No. IRCT20161205031252N8). This study adheres to CONSORT guidelines.

Radioprotective effects of montelukast, a selective leukotriene CysLT1 receptor antagonist, against nephrotoxicity induced by gamma radiation in mice.

PURPOSE: In this study, we evaluated the renal protective effects of montelukast (MLK) against ionizing radiation (IR) induced nephrotoxicity in mice. MATERIALS AND METHODS: Radioprotective effects of MLK were assessed by biochemical analysis including measurements of kidney malondialdehyde (MDA), reduced glutathione (GSH), and serum creatinine and urea levels. Besides, for further evaluation of protective effects of MLK on renal system, 99m Tc-dimercaptosuccinic acid (DMSA) has been applied. The total antioxidant capacity of MLK was measured by using 1,1-diphenyl-2-picryl hydrazyl radical reagents and compared with butylated hydroxyl toluene standard antioxidant. RESULTS: The biochemical evaluation revealed that better results have been achieved for the groups administered with MLK than the only radiation group. Besides only IR-treated mice group, those treated with MLK demonstrated a significant decrease in urea and creatinine levels. Statistically, significant differences of MDA and SHG levels (P < .05) were found between the radiation group and MLK plus IR-treated group. Also, 99m Tc-DMSA kidney uptake value (%ID/g) was observed lower for MLK plus IR-treated mice group than only radiation-treated mice group. CONCLUSIONS: According to our findings, MLK has a potential role to be used as a renal protective agent against gamma radiation in radiotherapy.

Comparison between Brush Cytology and Forceps Biopsy under Fluoroscopic Guidance for the Diagnosis of Proximal Cholangiocarcinoma.

BACKGROUND Cholangiocarcinoma is the second most common malignant liver cancer. Its early diagnosis plays an important role in the success of treatment. The aim of this study was to compare the use of cold forceps biopsy without cholangioscopy with brush cytology in the diagnosis of cholangiocarcinoma. METHODS In this prospective study, we enrolled 19 patients. Endoscopic retrograde cholangiopancreatography (ERCP) was performed for all individuals. Sampling was performed from the narrowing site using the brush method. Then, a cold forceps biopsy was performed under fluoroscopy. RESULTS The mean age of the patients was 63.31 ± 11.12 years and most of them were men (63.16 %). The brush cytology and the cold forceps biopsy diagnosed 31.85% and 68.42% of the samples as cholangiocarcinoma, respectively. According to the McNemar test, there was a statistically significant difference between the diagnostic results of the brush cytology and cold forceps biopsy. So that more cholangiocarcinoma cases were diagnosed using forceps biopsy (p = 0.016). No complications such as perforation, bleeding, cholangitis, and leakage were reported during the cold forceps procedure. CONCLUSION Cold forceps biopsy under fluoroscopy is better than cytology brush in the diagnosis of proximal cholangiocarcinoma. It is recommended to be used as a low-cost alternative in cases where cholangioscopy is not available.

Recent developments in peptide-based SPECT radiopharmaceuticals for breast tumor targeting.

Breast cancer deaths occur mainly because of poor diagnosis in early stages that lead to tumor metastasis in advanced stages. Developing a high-sensitive early-stage breast cancer diagnostic tool based on single photon emission computer tomography (SPECT) and positron emission tomography (PET) are urgent. There are several evidences to demonstrate the prominent roles of specific receptors overexpression in tumor initiation and progression of breast cancer. Targeting of specific receptor with radiolabeled biomolecule is a suitable tool for early diagnosis of breast cancer. In recent years, investigators have paid their attention in the development of peptide-based radiopharmaceuticals due to their favorable pharmacokinetics that offer diagnostic applications for breast cancer imaging. Various characterizing techniques permit the preparation of variety of peptides that allow efficiently labeling with clinically useful SPECT radionuclides such as 99mTc, 123I and 111In without compromising biological properties. In this review, we focus on the recent developments in use of peptide-based SPECT radiopharmaceuticals for breast cancer targeting and imaging.

99mTc-(tricine)-HYNIC-Lys-FROP Peptide for Breast Tumor Targeting.

BACKGROUND: Breast cancer is a malignant disease with high mortality rate among women in the world. It is necessary to diagnose breast cancer at the early stage before it metastasizes in patients. OBJECTIVE: The aim of this study is the evaluation of 99mTc-(tricine)-HYNIC-Lys-FROP for breast tumor imaging. METHOD: Lys-FROP peptide was labeled with 99mTc using HYNIC as chelator and tricine as co-ligand. Specific binding of this radiolabeled peptide on breast cancerous cell was assessed in different cell lines as well as in tumor-bearing mice. RESULTS: HYNIC-Lys-FROP peptide was labeled with 99mTc at radiochemical purity more than 99%. It was observed high stability in normal saline and serum about 95%. The highest cellular uptake was observed in MCF-7 breast tumor cells treated with 99mTc-(tricine)-HYNIC-Lys-FROP as compared to other cell lines (lung, ovarian, T47D breast cancer cell lines). Biodistribution results in female MCF-7 tumor-bearing mice showed the relatively high tumor uptake and tumor-muscle ratio as 3.82 ± 0.66 after 15 min post-injection of 99mTc-(tricine)- HYNIC-Lys-FROP. Tumor uptake was reduced in mice that were co-injected with excess of unlabeled peptide to be 0.91 ± 0.08. CONCLUSION: Findings showed this radiolabeled peptide is a promising candidate for tumor targeting and molecular imaging of breast cancer.

99mTc-HYNIC-(tricine/EDDA)-FROP peptide for MCF-7 breast tumor targeting and imaging.

BACKGROUND: Breast cancer is the most common malignancy among women in the world. Development of novel tumor-specific radiopharmaceuticals for early breast tumor diagnosis is highly desirable. In this study we developed 99mTc-HYNIC-(tricine/EDDA)-Lys-FROP peptide with the ability of specific binding to MCF-7 breast tumor. METHODS: The FROP-1 peptide was conjugated with the bifunctional chelator hydrazinonicotinamide (HYNIC) and labeled with 99mTc using tricine/EDDA co-ligand. The cellular specific binding of 99mTc-HYNIC-FROP was evaluated on different cell lines as well as with blocking experiment on MCF-7 (human breast adenocarcinoma). The tumor targeting and imaging of this labeled peptide were performed on MCF-7 tumor bearing mice. RESULTS: Radiochemical purity for 99mTc-HYNIC-(tricine/EDDA)-FROP was 99% which was determined with ITLC method. This radiolabeled peptide showed high stability in normal saline and serum about 98% which was monitored with HPLC method. In saturation binding experiments, the binding constant (Kd) to MCF-7 cells was determined to be 158 nM. Biodistribution results revealed that the 99mTc-HYNIC-FROP was mainly exerted from urinary route. The maximum tumor uptake was found after 30 min post injection (p.i.); however maximum tumor/muscle ratio was seen at 15 min p.i. The tumor uptake of this labeled peptide was specific and blocked by co-injection of excess FROP. According to the planar gamma imaging result, tumor was clearly visible due to the tumor uptake of 99mTc-HYNIC-(tricine/EDDA)-FROP in mouse after 15 min p.i. CONCLUSIONS: The 99mTc-HYNIC-(tricine/EDDA)-FROP is considered a promising probe with high specific binding to MCF-7 breast cancer cells.