Placental infection with SARS-CoV-2, analysis of 16 cases and literature review.

PURPOSE: Since December 2019, the whole world has been affected by coronavirus [severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)]. However, the effects of COVID-19 infection on pregnancy and fetal transmission are still unclear. Therefore, this study was conducted to evaluate placenta samples regarding detection of SARS-CoV-2 RNA in women affected with COVID-19. METHOD: This study was a part of a cohort study carried out on pregnant women with a diagnosis of COVID-19 infection who had been admitted to the Imam Reza Hospital in Mashhad, Iran, from March 20 to August 5, 2020. Clinical and laboratory information of all the patients was collected and chest computed tomography (CT) scans were reviewed. Totally, 16 placental tissue were prepared for real time polymerase chain reaction (RT-PCR) testing. All samples were tested by PowerChek PCR real-time kit (South Korea) with 2 target genes (E gene and Rd Rp gene), and Pishtaz Teb kit, (Iran) with 2 target genes (N gene and RdRp gene). RESULT: In the first RT-PCR kit by PowerChek kit, 6 samples were positive for a single gene (E gene) and 2 samples were positive for both genes (E gene and Rd Rp gene). In the second RT-PCR kit by Pishtaz Teb kit, 3 samples were positive for two genes (N gene and RdRp gene). CONCLUSION: This present study showed that infection of placenta with SARS-CoV-2 may occur in pregnancy. However, whether this infection leads to neonatal infection and serious complication in pregnancy remains unclear.

Prognostic role of follicular fluid tumor necrosis factor alpha in the risk of early ovarian hyperstimulation syndrome.

BACKGROUND: Ovarian hyperstimulation syndrome (OHSS) is an iatrogenic condition characterized by capillary hyperpermeability which can be predicted by preovulatory ovarian responses such as number of follicles. A variety of cytokines are thought to be involved in pathophysiology of this syndrome. METHODS: A prospective cohort study invloving sixty intracytoplasmic sperm injection (ICSI) patients. On the day of hCG injection, we explored the threshold of larger follicles ≥11 mm diameter with a count of ≥18 follicles for the high-risk moderate-to-severe OHSS and 13-18 follicles for the low-risk moderate-to-severe OHSS. Whereas larger follicles count of less than 13 were classified as normoresponders. Pooled follicular fluid (FF) samples of each patient were collected on the day of oocyte retrieval. Magnetic multiplex immunoassay was explored to measure the concentrations of some intrafollicular cytokines including: GM-CSF, INF-γ, TNF-α, IL-10, CXCL8/IL-8, IL-6, IL-5, IL-4, IL-2, and IL-1ß. All sixty patients underwent controlled ovarian hyperstimulation (COH) with either GnRH agonist or antagonist protocols. RESULTS: Intrafollicular TNF-α concentration was significantly different (p < 0.05) in the high-risk moderate-to-severe OHSS patients compared to low-risk moderate-to-severe OHSS patients and normoresponders. TNF-α in FF had a negative correlation with the chance of high-risk moderate-to-severe OHSS. The differences in the risk of OHSS between patients who received GnRH agonist or antagonist were not significant (p > 0.05). CONCLUSIONS: In accordance to the negative correlation of TNF-α and high risk of early OHSS, we did not expect TNF-α to play a role in increasing vascular permeability in ovarian tissues. In addition, the risk of early moderate-to-severe OHSS was not affected by different GnRH superovulation protocols.

IL-5 in follicular fluid as a negative predictor of the intracytoplasmic sperm injection outcome.

PURPOSE: To determine the prognostic value of intrafollicular concentrations of some cytokines from women undergoing ovarian stimulation in the outcome of intracytoplasmic sperm injection/embryo transfer (ICSI/ET) cycles. METHODS: A total of 80 patients were included in this study following ovarian stimulation and ICSI. Follicular fluids (FF) were collected at the day of oocyte retrieval. Ten cytokines including: tumor necrosis factor- alpha (TNF-α), interleukin (IL)-1ß, IL-2, IL-4, IL-5, IL-6, CXCL8/IL-8, IL-10, granulocyte-macrophage colony stimulating factor (GM-CSF), and interferon gamma (IFN-γ) were measured using magnetic multiplex immunoassays. RESULTS: Only the concentration of IL-5, IL-4, and GM-CSF in FF were significantly different (p < 0.05) between ICSI cycles that resulted in pregnancy and those that failed. Elevated FF IL-5 levels were associated with poor oocyte quality, which decreases the chance of both biochemical and clinical pregnancy. Higher FF GM-CSF associated with decrease of mature oocytes, while higher FF IL-4 concentrations were linked to good ICSI outcome through increased fertilization rate. CONCLUSIONS: The elevated intrafollicular concentrations of IL-5 seem to be a negative predictor to the pregnancy outcome in ICSI cycles.

Adenomyomas of the Uterine Cervix in the First-Trimester of Pregnancy: A Case Report.

Cervical adenomyomas of endocervical type (endocervical adenomyomas) are very rare benign lesions. Here we report the case of a 33-year-old woman who referred to the Perinatology Clinic of Ommolbanin Hospital (Mashhad, Iran) in September 2017. The patient was 8 weeks pregnant and complained of spotting and feeling a mass protruding from her vagina for 2 months. Physical examination revealed the presence of three masses of approximately 10 cm in the vagina, which were treated surgically. Histopathological examination of the excised specimen showed the presence of glands lined by a single layer of endocervical-type mucinous epithelium with smooth muscle fibers. Clinicians should be aware of such lesions in order to differentiate them from other malignancies and to individualize treatment.

Morphological diversity of cancer cells predicts prognosis across tumor types.

BACKGROUND: Intratumor heterogeneity drives disease progression and treatment resistance, which can lead to poor patient outcomes. Here, we present a computational approach for quantification of cancer cell diversity in routine hematoxylin-eosin-stained histopathology images. METHODS: We analyzed publicly available digitized whole-slide hematoxylin-eosin images for 2000 patients. Four tumor types were included: lung, head and neck, colon, and rectal cancers, representing major histology subtypes (adenocarcinomas and squamous cell carcinomas). We performed single-cell analysis on hematoxylin-eosin images and trained a deep convolutional autoencoder to automatically learn feature representations of individual cancer nuclei. We then computed features of intranuclear variability and internuclear diversity to quantify tumor heterogeneity. Finally, we used these features to build a machine-learning model to predict patient prognosis. RESULTS: A total of 68 million cancer cells were segmented and analyzed for nuclear image features. We discovered multiple morphological subtypes of cancer cells (range = 15-20) that co-exist within the same tumor, each with distinct phenotypic characteristics. Moreover, we showed that a higher morphological diversity is associated with chromosome instability and genomic aneuploidy. A machine-learning model based on morphological diversity demonstrated independent prognostic values across tumor types (hazard ratio range = 1.62-3.23, P < .035) in validation cohorts and further improved prognostication when combined with clinical risk factors. CONCLUSIONS: Our study provides a practical approach for quantifying intratumor heterogeneity based on routine histopathology images. The cancer cell diversity score can be used to refine risk stratification and inform personalized treatment strategies.

Serum gastrin 17, pepsinogen I and pepsinogen II in atrophic gastritis patients living in North-East of Iran.

BACKGROUND: Gastric carcinoma is the second most common cause of cancer-related death in Iran. It is well-known that atrophic gastritis is a major risk factor for gastric cancer, which leads to variations in the serum levels of gastrin 17 (G-17), pepsinogen I (P-I), and pepsinogen II (P-II). The aim of this study was to investigate the diagnostic accuracy of these serum biomarkers in the early detection of atrophic gastritis. MATERIALS AND METHODS: A total of 132 dyspeptic patients underwent upper endoscopy and biopsies were taken. The biopsy specimens were evaluated as the gold standard according to operative link for gastritis assessment staging system. Serum levels of G-17, P-I, and P-II were investigated using enzyme-linked immunosorbent assay. Receiver operating characteristic (ROC) analysis was used to calculate the diagnostic indices and optimal cut-off values using Statistical Package for the Social Sciences SPSS statistical software. RESULTS: A total of 67 men and 65 women were analyzed, among which 48 (36.4%) had atrophic gastritis. The mean age was 45.8 (±15.8) years. ROC curve analysis demonstrated that the biomarkers (including pepsinogen I/II [P-I/II] ratio), except for P-I, are diagnostically significant in detecting gastric atrophy. The area under the curve (95% confidence interval [CI]) for G-17, P-I, P-II, and P-I/II ratio were 0.65 (0.55-0.76), 0.42 (0.32-0.53), 0.62 (0.52-0.72), and 0.61 (0.50-0.72), respectively. However, the diagnostic indices were low (sensitivity <50%, specificity < 90%). The prevalence of Helicobacter pylori infection was significantly higher in patients with atrophy against those without atrophy (75.0% vs. 57.4%, P value < 0.0001). CONCLUSION: In the studied population, the serum biomarkers of atrophic gastritis are not useful screening tests due to their low sensitivity.

Crocus sativus (saffron) petals extract and its active ingredient, anthocyanin improves ovarian dysfunction, regulation of inflammatory genes and antioxidant factors in testosterone-induced PCOS mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Saffron petal has traditionally been used to treat a variety of diseases, such as gynecological disease such as primary dysmenorrhea and premenstrual tension. Polycystic Ovary Syndrome (PCOS) is a form of gynecological disease that causes amenorrhea, infertility, menopausal and urogenital disorders. This disease may be treated with saffron petals. AIM OF THE STUDY: In this study, the effects of saffron petal extract (SPE) and saffron petal anthocyanins (SPA) on ovarian hormones, steroidogenic enzymes, ovarian dysfunction, regulation of anti-inflammatory genes, and antioxidant factors in female PCOS mice were studied. METHODS AND RESULTS: The PCOS mouse model was induced by testosterone enanthate (TE), and an in vivo evaluation of whether the dietary consumption of SPE and SPA improved the PCOS-like symptoms was conducted. The luteinizing hormone (LH), testosterone, and estrogen levels increased in PCOS mice, but decreased following SPE and SPA treatment. In the PCOS mice, the reduced follicular-stimulating hormone (FSH) progesterone levels were restored to that of normal controls with SPE and SPA treatment in serum. The transcription level(s) of gonadotropin receptors (Fshr and Lhr), steroid receptors (Pgr, and Esr1), inflammatory markers (TNFα, IL1ß, IL6 and IL18), inflammatory-related factors (NF-κB, NF-κB p65, IκB) and antioxidant enzymes (GPx, SOD, CAT, GST, and GSH) changed under the PCOS condition. Moreover, they were regulated by SPE and SPA treatment in PCOS mice ovaries. The reproductive tissues of TE induced PCOS mice were restored into estrogenic conditions from androgen environments. The study of antioxidant activity of SPE and SPA using FRAP and DPPH tests showed high antioxidant activity. CONCLUSION: These results suggest that SPE and SPA ameliorates symptoms of PCOS by improving dysregulation of ovarian steroids, steroidogenic, antioxidant enzymes and inflammatory markers in PCOS mice.

Investigating the Effect of Crocus sativus (Saffron) Petal Hydro-alcoholic Extract on Ovarian Follicle, Inflammatory Markers, and Antioxidant Enzymes in Mice Model of Polycystic Ovary Syndrome.

Background: Saffron petals have traditionally been used to treat a variety of diseases, such as gynecological diseases, primary dysmenorrhea, and premenstrual syndrome. Polycystic ovary syndrome (PCOS) is a kind of gynecological disease that causes infertility, menopausal and urogenital disorders and saffron petals seem to be an efficient treatment for such disorders. Methods: NMRI mice (total=60, each group n=12) were divided into control, PCOS, and the treatment groups. PCOS and treatment groups were injected with testosterone enanthate (TE=1 mg/kg). After 4 weeks, the treatment group was treated with Saffron Petal Extract (SPE) for 14 days. Ovary and blood samples were collected for histological and serological analyses, and expression of NF-κB, NF-κB p65, and IκB genes was analyzed. Finally, data were analyzed using one-way ANOVA (p<0.05). Results: In this study, the number of corpus luteum decreased in PCOS mice (p<0.001) but increased with SPE treatment (p<0.05, p<0.01, p<0.001). The number of cystic follicles increased in PCOS mice (p<0.001), but decreased with SPE treatment (p<0.05, p<0.001). TNFα, IL1ß, IL6, IL18, and CRP levels increased in PCOS mice (p<0.001), but decreased following SPE treatment (p<0.05, p<0.001). Glutathione (GSH) and glutathione S-transferase (GST) serum levels decreased in PCOS mice (p<0.001), but increased with SPE treatment (p<0.05, p<0.001). The transcriptional level (s) of NF-κB, NF-κB p65, IκB genes changed in PCOS condition (p<0.001), and were regulated by SPE treatment (p<0.05, p<0.01 and p<0.001). Conclusion: The present study shows that SPE improved the PCOS symptoms in mice via increasing antioxidant factors and reducing inflammatory markers in serum.

Evaluation of cytokine levels as possible predicting elements in patients with chronic lymphocytic leukemia.

OBJECTIVE: This study aimed to assess the patterns of serum cytokines in chronic lymphocytic leukemia patients at baseline and post-chemotherapy and investigate their association with response to treatment and chronic lymphocytic leukemia prognosis. METHODS: Blood samples were taken from 32 subjects at their first medical visit after being diagnosed with chronic lymphocytic leukemia and 1 year after chemotherapy. Then, levels of cytokines and blood parameters in peripheral blood were measured. Correlation analysis was used to assess the indexes before and after chemotherapy as well as at different disease stages. RESULTS: Most of the patients (45.80%) had stages I and III before initiation of treatment and after treatment, respectively. There were significant differences between levels of interleukin (IL)-6 (p=0.006) and IL-10 (p=0.009) before and after treatment. Notably, the difference in IL-10 levels before and after treatment was significantly higher in the advanced stages compared to that in the non-advanced stages (p=0.007). IL-6 and IL-10 were also higher in the expired patients compared to the survived cases. CONCLUSIONS: Cytokines such as IL-6 and IL-10 may be considered predicting factors for chronic lymphocytic leukemia prognosis.

Evaluation of IL-3, IL-5, and IL-6 concentration in the follicular fluid of women with endometriosis: A cross-sectional study.

Background: Endometriosis is associated with abnormal immunologic responses and combined inflammatory and anti-inflammatory conditions. Objective: This study aims to investigate follicular fluid (FF) concentration of interleukin (IL)-3, IL-5, and IL-6 in women with and without endometriosis. Materials and Methods: In this cross-sectionalstudy 68 women who were referred to the in vitro fertilization center of Imam Reza hospital in Mashhad during 2018 were selected randomly. Leaves of cytokines in the FF samples were evaluated in the endometriosis and the control group (n = 34/each). The diagnostic accuracy of cytokines and clinical characteristics were evaluated. Results: IL-3 and IL-6 were significantly changed in the FF of the women with endometriosis compared with the control group (p = 0.04, and p < 0.01, respectively), and the mean concentration of IL-5 in the endometriosis group was lower than in the control group (p = 0.5), but this was not significant. There were significant differences in the menstrual cycle, dyspareunia, and dysmenorrhea between the groups (p < 0.01, p = 0.04, and p = 0.02, respectively). The diagnostic accuracy of IL-3 and IL-6 in the FF was low, with the area under the curve of 0.614 and 0.645, respectively. Conclusion: Although none of the cytokines had a predictive value for endometriosis, the decreased levels of IL-3 and increased levels of IL-6 in the FF samples of women with endometriosis, and risk factors, including irregular menstrual cycle, dyspareunia, and dysmenorrhea, could be associated with the pathogenesis of this painful disease.

Effects of Sertraline on Spermatogenesis of Male Rats and its Reversibility after Terminating the Drug.

PURPOSE: The purpose of this research was to studding the effects of Sertraline on spermatogenesis of male rats and whether these probable effects are constant or provisional after terminating the drug. MATERIALS AND METHODS: In this study, 32  two-month old male Wistar albino rats were equally divided into the Sertraline-treated and the control groups. The drug group was gavaged with Sertraline daily while the control group was gavaged with water at the same volume. After 80 days, half of the rats in each group were selected randomly for hormonal evaluations and bilateral orchiectomy. Histological and hormonal evaluations were performed. The remaining half of rats were kept alive for 90 more days without intervention and then underwent hormonal evaluation and bilateral orchiectomy in a similar fashion. RESULTS: There was no difference between the testes histology and pathology of the sertraline-treated and the control groups.  There was a significant decrease in serum FSH in the Sertraline-treated group compared to the control group (P <0.05). However, this decline appeared to be reversible following termination of exposure to Sertraline. FSH returned to pretreatment levels in the remaining treated rats following 90 days of treatment cessation.  Conclusion: Within the time-frame studied, Sertraline can induce transitory changes in serum FSH of male rats without concomitant spermatogenic changes within the testes.  This hormonal change appears to be reversible following withholding of Sertraline. The long-term effect of Sertraline usage on hormonal status and spermatogenesis in rats needs further investigation.

Familial lecithin-cholesterol acyltransferase deficiency.

Familial lecithin-cholesterol acyltransferase deficiency is an uncommon autosomal recessive disorder from a heritable defect in esterification of plasma cholesterol. In 1968, the disease was described by Gjone and Norum in Norway. Our case was a 38-year-old woman. Her disease was manifested by presence of lower extremities edema, proteinuria, corneal opacities, increased plasma cholesterol, and hemolytic anemia. Suspicion of the disease was based on renal biopsy, which revealed mesangial expansion and capillary wall widening with clusters of foamy cells in the mesangium. Immunofluorescence study was nonspecific, but specific findings of electron microscopy showed deposition of lipid in the glomerular basement membrane and mesangium. This is the first report of lecithin-cholesterol acyltransferase deficiency in Iran.The diagnosis was confirmed by a low high-density lipoprotein cholesterol concentration, decreased activity of lecithin-cholesterol acyltransferase in plasma, and positive familial history of the disease.

Association of IL-1 and TNF-α Levels in Endometrial Secretion and Success of Embryo Transfer in IVF/ICSI Cycles.

BACKGROUND: In this work, we have determined the levels of interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-α), which function as cytokines in endometrial receptivity, through the endometrial secretion within the eligible individuals and thus studied their relationships with the success or failure of pregnancy in in vitro fertilization/intra cytoplasmic sperm injection (IVF/ICSI) cycles. MATERIALS AND METHODS: In this prospective study, 76 women were selected for their first IVF/ICSI and met the study inclusion criteria. All of the patients have undergone the endometrial secretion aspiration prior to performing the oocyte collection. The levels of IL-1and TNF-α were analyzed by the means of enzyme-linked immunosorbent assay method, using special standard kits. The patients were requested to undergo the serum human chorionic gonadotropin measurements and ultrasound evaluation for the purpose of detecting successful implantations and pregnancies. RESULTS: Among the 76 subjects of the study, 33 (43.4%) patients had a positive beta-human chorionic gonadotropin (ß-hCG) and 44 (56.6%) resulted in a negative ß-hCG. It should be also noted that through the patients with positive ß-hCG, 23 (30.3%) of them displayed fetal heart rate in their transvaginal sonography (TVS). Compared to the group with failed pregnancies and their cytokine levels, we perceived a higher concentration of IL-1 in the group containing successful chemical pregnancies (P=0.00). However, there was no significant difference in terms of clinical pregnancy in the IL-1 levels between the two groups (P=0.06). In addition, there was not any notable difference in the levels of TNF-α between the two groups, neither in terms of chemical nor clinical pregnancy (P=0.8 and P=0.6, respectively). CONCLUSION: The current study suggests that higher concentrations of IL-1 in endometrial secretions could be associated with improved endometrial receptivity and IVF outcome. With regards to TNF-α, no statistically significant difference was observed between the groups of with and without successful pregnancies.

Optimizing denaturing HPLC as a robust technique for identification of Short Tandem Repeats (STR) in forensic medicine.

INTRODUCTION: Short Tandem Repeats (STRs) are defined as short lengths of 2-7 base pairs spreading through human genome which due to their highly diverse individually distribution are widely applied for identity detection and other forensic medicine purposes. Burdening considerable costs by the conventional methods such as capillary electrophoresis, we aimed to compare concomitant usage of multiplex PCR and denaturing high-performance liquid chromatography (DHPLC) as cheap, fast, highly accurate, and more accessible methods, with capillary electrophoresis (CE) to evaluate their potential for early screening of STRs. MATERIALS AND METHODS: The present study randomly included 20 blood samples from the subjects referred to forensic medicine of Semnan, Iran. According to the size and allele frequency, we selected 8 major STR loci including CSF1PO, VWA, D18S51, TPOX, Amelogenin, FGA, SE33, and Penta D. A quad-STR multiplex PCR was performed for each locus and the PCR products were then analyzed using DHPLC machine and compared with the basic genetic properties obtained by capillary electrophoresis. RESULTS: By optimizing the PCR and DHPLC conditions, our findings suggest this strategy as an effective method for STR detection. The genotypes were determined using size of loci which led to comparable results with capillary electrophoresis confirming an insignificant variation in the detection of TOPX, Amelogenin, CSF1PO, and D18S5 (p = 0.331), but discrepant results for FGA and VWA loci (p = 0.002). CONCLUSION: Our study proposed DHPLC method as an effective screening method to characterize TOPX, Amelogenin, CSF1PO, and D18S51 as frequently used STR loci during identity detection in forensic medicine.

Cinnamaldehyde improves methamphetamine-induced spatial learning and memory deficits and restores ERK signaling in the rat prefrontal cortex.

OBJECTIVES: Methamphetamine is a stimulant compound that penetrates readily into the central nervous system. Repeated exposure to methamphetamine leads to damage in the dopaminergic and serotonergic axons of selected brain regions. Previous studies showed that cinnamaldehyde improved memory impairment in animals. In the present study, we aimed to elucidate the effects of cinnamaldehyde on methamphetamine-induced memory impairment in rats. MATERIALS AND METHODS: Male Wistar rats received methamphetamine (10 mg/kg, intraperitoneally) for 7 days. Thirty minutes before each injection, animals were given cinnamaldehyde (20, 40, or 80 mg/kg) or rivastigmine (1 mg/kg). The spatial learning and memory were examined using the Morris water maze test. The expression of extracellular signal-regulated kinase (ERK) phosphorylation in the frontal cortex and hippocampus was also detected by immunohistochemical method. RESULTS: Administration of methamphetamine increased the latency to find the platform in the learning phase, while administration of cinnamaldehyde (40 mg/kg) or rivastigmine before methamphetamine reversed the increased latency. Administration of cinnamaldehyde, at the dose of 40 mg/kg with methamphetamine, increased the time and distance traveled in the target quadrant in comparison with the amphetamine group. Moreover, the methamphetamine and cinnamaldehyde-treated group had higher expression of phosphorylated ERK1/2 in the prefrontal cortex in comparison with the methamphetamine-treated animals. CONCLUSION: The present data demonstrated that repeated METH administration impaired cognitive performance through the ERK pathway and decreased the phosphorylation of ERK1/2 in the prefrontal cortex while administration of cinnamaldehyde restored both effects. Accordingly, cinnamaldehyde may be a valuable therapeutic tool for the treatment of cognitive deficits associated with methamphetamine consumption.

Modified PAMAM vehicles for effective TRAIL gene delivery to colon adenocarcinoma: in vitro and in vivo evaluation.

TRAIL (tumour necrosis factor-related apoptosis-inducing ligand) gene therapy is considered as one of the promising approaches for cancer treatment. Polyamidoamine (PAMAM) is one of the most extensively applied polymeric vector in gene delivery. In the current study, PAMAM (G4 and G5) dendrimers were modified with alkyl-carboxylate chain, PEG and cholesteryl chloroformate in order to enhance transfection efficiency through overcoming extracellular and intracellular barriers while reducing PAMAM cytotoxicity. Gene delivery efficiency of synthetized vectors was evaluated by both GFP (green fluorescent protein) reporter gene and TRAIL plasmid in colon cancer cells, in vitro and in vivo. The obtained results demonstrated that PAMAM G4-alkyl-PEG (3%)-Chol (5%)-TRAIL complexes at C/P ratio 4 could significantly increase cell death (29.45%) in comparison with unmodified PAMAM vector (15.5%). Moreover, in vivo study in C26 tumor-bearing BALB/c mice suggested that the prepared non-toxic safe vector could inhibit the tumor growth. This study represented the potent vehicle based on cholesterol-grafted PAMAM dendrimers with alkyl-PEG modification for efficient gene delivery in vitro and in vivo.

Role of the Zeta Method in Intracytoplasmic Sperm Injection Outcomes in High Sperm DNA Fragmentation in Oligoasthenozoospermic Men.

BACKGROUND: New methods are needed to optimize intracytoplasmic sperm injection (ICSI) outcomes in oligoasthenozoospermic (OAS) men. We evaluated the level of DNA fragment index (DFI) in OAS men and its impact on ICSI outcomes. In addition, we used the zeta potential method for sperm selection to investigate the efficacy of this technique in improving ICSI outcomes. MATERIALS AND METHODS: This cross-sectional study was performed on 95 couples. Sperm parameters and sperm DNA fragmentation (SDF) were measured. The couples were divided into the following 3 groups: group I (n=30) where SDF was between 15% and 30%, and routine sperm was selected on the basis of motility and morphology; group II (n=34) where SDF was more than 30%, and the routine sperm selection method was applied on the basis of motility and morphology; and group III (n=31) where SDF was more than 30%, and the sperm selection was performed on the basis of the zeta method. The fertilization rate, embryo development, embryo quality, and implantation rate were evaluated in these 3 groups. RESULTS: The fertilization rate was significantly higher in group I compared with group II (P<0.05). The embryo development rate in group I was significantly higher than that in group II (P<0.001) and group III (P<0.05), and it was significantly lower in group II compared with group III (P<0.05). The embryo quality was higher in group III compared with group II (P<0.01). The implantation rate in group I was significantly higher than that in group II (P<0.05) and group III (P<0.05). CONCLUSIONS: The present study indicated that a higher level of SDF has an adverse effect on the ICSI outcome. Furthermore, the zeta potential technique can be a useful method for sperm selection in OAS men.

Injury to skeletal muscle of mice following acute and sub-acute pregabalin exposure.

OBJECTIVES: Pregabalin (PGB) is a new antiepileptic drug that has received FDA approval for patient who suffers from central neuropathic pain, partial seizures, generalized anxiety disorder, fibromyalgia and sleep disorders. This study was undertaken to evaluate the possible adverse effects of PGB on the muscular system of mice. MATERIALS AND METHODS: To evaluate the effect of PGB on skeletal muscle, the animals were exposed to a single dose of 1, 2 or 5 g /kg or daily doses of 20, 40 or 80 mg/kg for 21 days, intraperitoneally (IP). Twaenty-four hr after the last drug administration, all animals were sacrificed. The level of fast-twitch skeletal muscle troponin I and CK-MM activity were evaluated in blood as an indicator of muscle injury. Skeletal muscle pathological findings were also reported as scores ranging from 1 to 3 based on the observed lesion. RESULTS: In the acute and sub-acute toxicity assay IP injection of PGB significantly increased the activity and levels of CK-MM and fsTnI compared to the control group. Sub-acute exposure to PGB caused damages that include muscle atrophy, infiltration of inflammatory cells and cell degeneration. CONCLUSION: PGB administration especially in long term care causes muscle atrophy with infiltration of inflammatory cells and cell degeneration. The fsTnI and CK-MM are reliable markers in PGB-related muscle injury. The exact mechanisms behind the muscular damage are unclear and necessitate further investigations.

Evaluation of cytokine levels as possible predicting elements in patients with chronic lymphocytic leukemia

SUMMARY OBJECTIVE: This study aimed to assess the patterns of serum cytokines in chronic lymphocytic leukemia patients at baseline and post-chemotherapy and investigate their association with response to treatment and chronic lymphocytic leukemia prognosis. METHODS: Blood samples were taken from 32 subjects at their first medical visit after being diagnosed with chronic lymphocytic leukemia and 1 year after chemotherapy. Then, levels of cytokines and blood parameters in peripheral blood were measured. Correlation analysis was used to assess the indexes before and after chemotherapy as well as at different disease stages. RESULTS: Most of the patients (45.80%) had stages I and III before initiation of treatment and after treatment, respectively. There were significant differences between levels of interleukin (IL)-6 (p=0.006) and IL-10 (p=0.009) before and after treatment. Notably, the difference in IL-10 levels before and after treatment was significantly higher in the advanced stages compared to that in the non-advanced stages (p=0.007). IL-6 and IL-10 were also higher in the expired patients compared to the survived cases. CONCLUSIONS: Cytokines such as IL-6 and IL-10 may be considered predicting factors for chronic lymphocytic leukemia prognosis.

Intratumoral CD68-, CD117-, CD56-, and CD1a-positive immune cells and the survival of Iranian patients with non-metastatic intestinal-type gastric carcinoma.

The purpose of this study was to investigate the prognostic significance of intratumoral immune cell counts in Iranian gastric cancer patients. A historical cohort study was conducted on fifty patients with non-metastatic intestinal-type gastric adenocarcinoma who underwent curative gastrectomy during 2004-2008 in Imam-Reza Hospital, Mashhad University of Medical Sciences. Immunohistochemistry (IHC) staining for CD56, CD68, CD117 and CD1a was performed to detect natural killer cells, macrophages, mast cells and Langerhans cells, respectively. The immune cells were counted, and the patients were then stratified into low or high immune cell counts. The prognostic significance of this grouping was analyzed using the Kaplan Meier method and Cox proportional hazards regression modeling. Thirty eight (76%) male and twelve (24%) female patients were enrolled in the study with a mean (±SD) age of 66.0 (±9.2) years. The median survival time was 15.0 (95%CI: 5.5-24.5) months. Natural killer cells, mast cells and Langerhans cells showed a positive effect on survival, whereas the reverse was true for macrophages. Multivariate analysis showed that the independent prognostic factors were location of the tumor (cardia/non-cardia), stage, the presence of extra-cytoplasmic mucin, tumor associated macrophage status (low/high), and tumor associated Langerhans cell status (low/high). In the studied population, gastric carcinoma proved to have a very poor prognosis. Multivariate analysis showed that the prognostic effect of natural killer and mast cells in tumoral tissue were dependent on the Langerhans cell count, defending the theory that dendritic cells mediate other immunocytes activities.