Taleghani General Hospital

The ubiquitin-proteasome system is a major regulatory pathway of protein degradation and plays an important role in cellular division. Fbxw7 (or hCdc4), a member of the F-box family of proteins, which are substrate recognition components of the multisubunit ubiquitin ligase SCF (Skp1-Cdc53/Cullin-F-box-protein), has been shown to mediate the ubiquitin-dependent proteolysis of several oncoproteins including cyclin E1, c-Myc, c-Jun, and Notch. The oncogenic potential of Fbxw7 substrates, frequent allelic loss in human cancers, and demonstration that mutation of FBXW7 cooperates with p53 in mouse tumorigenesis have suggested that Fbxw7 could function as a tumor suppressor in human cancer. Here, we carry out an extensive genetic screen of primary tumors to evaluate the role of FBXW7 as a tumor suppressor in human tumorigenesis. Our results indicate that FBXW7 is inactivated by mutation in diverse human cancer types with an overall mutation frequency of approximately 6%. The highest mutation frequencies were found in tumors of the bile duct (cholangiocarcinomas, 35%), blood (T-cell acute lymphocytic leukemia, 31%), endometrium (9%), colon (9%), and stomach (6%). Approximately 43% of all mutations occur at two mutational "hotspots," which alter Arg residues (Arg465 and Arg479) that are critical for substrate recognition. Furthermore, we show that Fbxw7Arg465 hotspot mutant can abrogate wild-type Fbxw7 function through a dominant negative mechanism. Our study is the first comprehensive screen of FBXW7 mutations in various human malignancies and shows that FBXW7 is a general tumor suppressor in human cancer.

BACKGROUND: End-stage liver disease is a medical problem with high morbidity and mortality. We have investigated the feasibility, safety, and efficacy of using autologous mesenchymal stem cells (MSCs) as a treatment. METHODS: Eight patients (four hepatitis B, one hepatitis C, one alcoholic, and two cryptogenic) with end-stage liver disease having Model for End-Stage Liver Disease score > or =10 were included. Autologous MSCs were taken from iliac crest. Approximately, 30-50 million MSCs were proliferated and injected into peripheral or the portal vein. Liver function and clinical features were evaluated at baseline and 1, 2, 4, 8, and 24 weeks after injection. RESULTS: Treatment was well tolerated by all patients. Liver function improved as verified by the Model for End-Stage Liver Disease score, which decreased from 17.9+/-5.6 to 10.7+/-6.3 (P<0.05) and prothrombin complex from international normalized ratio 1.9+/-0.4 to 1.4+/-0.5 (P<0.05). Serum creatinine decreased from 114+/-35 to 80+/-18 micromol/l (P<0.05). Serum albumin changed from 30+/-5 to 33+/-5 g/l and bilirubin from 46+/-29 to 41+/-31 micromol/l. No adverse effects were noted. CONCLUSION: Our data show that MSCs injection can be used for the treatment of end-stage liver disease with satisfactory tolerability. Furthermore, this treatment may improve clinical indices of liver function in end-stage liver disease.

BACKGROUND: Chronic constipation is described as a common complication determined by difficult and/or rare passage of stool or both. The difference in definition of constipation has led to a wide range of reported prevalence (i.e., between 1% and 80%). Various factors are involved in the pathogenesis of the disease, including type of diet, genetic predisposition, colonic motility, absorption, social economic status, daily behaviors, and biological and pharmaceutical factors. Diagnostic and therapeutic options play a key role in the treatment of chronic constipation. There are still debates about the timing of these diagnostic and therapeutic algorithms. METHODS: A systematic and comprehensive search will be performed using MEDLINE, PubMed, EMBASE, AMED, the Cochrane Library and Google Scholar. Better understanding of the pathophysiology of chronic constipation and efficacy of pharmacological agent can help physicians for treating and managing symptoms.In this study, some of the old and new therapies in the treatment of chronic constipation have been studied based on the controlled studies and strong evidence. We are trying to address some of the controversial issues to manage the disease and to provide appropriate diagnostic options in an efficient and cost-effective way. RESULTS: The results of this systematic review will be published in a peer-reviewed journal. CONCLUSION: To our knowledge, our study will provide an overall estimate of chronic constipation to assess controversial issues, available diagnostic and therapeutic strategies of chronic constipation. ETHICS AND DISSEMINATION: Ethical approval and informed consent are not required, as the study will be a literature review and will not involve direct contact with patients or alterations to patient care.

Since 2000, many countries have achieved considerable success in improving child survival, but localized progress remains unclear. To inform efforts towards United Nations Sustainable Development Goal 3.2-to end preventable child deaths by 2030-we need consistently estimated data at the subnational level regarding child mortality rates and trends. Here we quantified, for the period 2000-2017, the subnational variation in mortality rates and number of deaths of neonates, infants and children under 5 years of age within 99 low- and middle-income countries using a geostatistical survival model. We estimated that 32% of children under 5 in these countries lived in districts that had attained rates of 25 or fewer child deaths per 1,000 live births by 2017, and that 58% of child deaths between 2000 and 2017 in these countries could have been averted in the absence of geographical inequality. This study enables the identification of high-mortality clusters, patterns of progress and geographical inequalities to inform appropriate investments and implementations that will help to improve the health of all populations.

BACKGROUND: Past research in population health trends has shown that injuries form a substantial burden of population health loss. Regular updates to injury burden assessments are critical. We report Global Burden of Disease (GBD) 2017 Study estimates on morbidity and mortality for all injuries. METHODS: We reviewed results for injuries from the GBD 2017 study. GBD 2017 measured injury-specific mortality and years of life lost (YLLs) using the Cause of Death Ensemble model. To measure non-fatal injuries, GBD 2017 modelled injury-specific incidence and converted this to prevalence and years lived with disability (YLDs). YLLs and YLDs were summed to calculate disability-adjusted life years (DALYs). FINDINGS: In 1990, there were 4 260 493 (4 085 700 to 4 396 138) injury deaths, which increased to 4 484 722 (4 332 010 to 4 585 554) deaths in 2017, while age-standardised mortality decreased from 1079 (1073 to 1086) to 738 (730 to 745) per 100 000. In 1990, there were 354 064 302 (95% uncertainty interval: 338 174 876 to 371 610 802) new cases of injury globally, which increased to 520 710 288 (493 430 247 to 547 988 635) new cases in 2017. During this time, age-standardised incidence decreased non-significantly from 6824 (6534 to 7147) to 6763 (6412 to 7118) per 100 000. Between 1990 and 2017, age-standardised DALYs decreased from 4947 (4655 to 5233) per 100 000 to 3267 (3058 to 3505). INTERPRETATION: Injuries are an important cause of health loss globally, though mortality has declined between 1990 and 2017. Future research in injury burden should focus on prevention in high-burden populations, improving data collection and ensuring access to medical care.

BACKGROUND: The global burden of road injuries is known to follow complex geographical, temporal and demographic patterns. While health loss from road injuries is a major topic of global importance, there has been no recent comprehensive assessment that includes estimates for every age group, sex and country over recent years. METHODS: We used results from the Global Burden of Disease (GBD) 2017 study to report incidence, prevalence, years lived with disability, deaths, years of life lost and disability-adjusted life years for all locations in the GBD 2017 hierarchy from 1990 to 2017 for road injuries. Second, we measured mortality-to-incidence ratios by location. Third, we assessed the distribution of the natures of injury (eg, traumatic brain injury) that result from each road injury. RESULTS: Globally, 1 243 068 (95% uncertainty interval 1 191 889 to 1 276 940) people died from road injuries in 2017 out of 54 192 330 (47 381 583 to 61 645 891) new cases of road injuries. Age-standardised incidence rates of road injuries increased between 1990 and 2017, while mortality rates decreased. Regionally, age-standardised mortality rates decreased in all but two regions, South Asia and Southern Latin America, where rates did not change significantly. Nine of 21 GBD regions experienced significant increases in age-standardised incidence rates, while 10 experienced significant decreases and two experienced no significant change. CONCLUSIONS: While road injury mortality has improved in recent decades, there are worsening rates of incidence and significant geographical heterogeneity. These findings indicate that more research is needed to better understand how road injuries can be prevented.

BACKGROUND: Although the effect of bisphosphonates on dental implant osseointegration is not clear, dental implant failures attributable to oral bisphosphonate therapy have been reported in patients with osteoporosis. PURPOSE: The aim of this study was to evaluate implant survival in patients with a history of bisphosphonate therapy in a retrospective survey. MATERIALS AND METHODS: A total of 46 ITI implants placed in 21 osteoporotic patients (females; average age 53 years, range 42-79 years) were evaluated with regard to probing depth, mobility, thread exposure, and bleeding on probing. All patients were under oral bisphosphonate therapy. RESULTS: None of implants showed mobility and all patients could be considered free from peri-implantitis. Time of bisphosphonate therapy before and after implant insertion showed no statistically significant influence on PD, BOP, and TE. Likewise, implant location, prosthetic type, and opposing dentition had no statistically significant influence on the clinical and radiological parameters of implants. CONCLUSION: Within the limitations of this study, it could be concluded that neither being on oral bisphosphonate treatment before implant placement nor starting bisphosphonate therapy after implant installation might jeopardize the successful osseointegration and clinical and radiographic condition of the implants.

BACKGROUND: Vitamin D deficiency in women diagnosed with polycystic ovary syndrome (PCOS) remarkably decreases the chance of pregnancy, which might be related to its impact on metabolic abnormalities in these patients. It is hypothesized that vitamin D supplementation influences metabolic profile of these patients and indirectly might affect fertility and the outcomes. Therefore, this study was conducted to determine the effects of vitamin D supplementation on the levels of anti-Müllerian hormone (AMH), metabolic profiles, and gene expression of insulin and lipid metabolism in infertile women with PCOS who were candidate for in vitro fertilization (IVF). METHODS: This study was a randomized, double-blinded, placebo-controlled trial conducted among 40 infertile women, aged 18-40 years, diagnosed with PCOS and was candidate for IVF. Participants were randomly assigned into two intervention groups for receiving either 50,000 IU vitamin D or placebo (n = 20 each group) every other week for 8 weeks. Gene expression for insulin and lipid metabolism was conducted using peripheral blood mononuclear cells (PBMCs) of women with PCOS, via RT-PCR method. RESULTS: Vitamin D supplementation led to a significant reduction in serum AMH (- 0.7 ± 1.2 vs. - 0.1 ± 0.5 ng/mL, P = 0.02), insulin levels (- 1.4 ± 1.6 vs. -0.3 ± 0.9 μIU/mL, P = 0.007), homeostatic model of assessment for insulin resistance (- 0.3 ± 0.3 vs. -0.1 ± 0.2, P = 0.008), and a significant increase in quantitative insulin sensitivity check index (+ 0.009 ± 0.01 vs. + 0.001 ± 0.004, P = 0.04), compared with the placebo. Moreover, following vitamin D supplementation there was a significant decrease in serum total- (- 5.1 ± 12.6 vs. + 2.9 ± 10.9 mg/dL, P = 0.03) and LDL-cholesterol levels (- 4.5 ± 10.3 vs. + 2.5 ± 10.6 mg/dL, P = 0.04) compared with the placebo. CONCLUSION: Overall, the findings of this trial supported that 50,000 IU vitamin D supplementation every other week for 8 weeks had beneficial effects on insulin metabolism, and lipid profile of infertile women with PCOS who are candidate for IVF. These benefits might not be evident upon having sufficient vitamin D levels. TRIAL REGISTRATION: This study was retrospectively registered in the Iranian website ( www.irct.ir ) for clinical trials registration ( http://www.irct.ir : IRCT20170513033941N27).

BACKGROUND: The more recent use of ultrasound scanning allows a direct measurement on unmodified skin, and is considered to be a reliable method for in vivo measurement of epidermal and dermal thickness. The objective of this study was to assess the influence of gender and age on the thickness and echo-density of skin measured by high frequency ultrasonography (HFUS). MATERIALS AND METHODS: This study was carried out on 30 healthy volunteers (17 female, 13 male) with age range of 24-61 years old. The thickness and echo-density of dermis as well as epidermal entrance echo thickness in five anatomic sites (cheek, neck, palm, dorsal foot, and sole) were measured using two different types of B mode HFUS, 22 and 50 MHz frequencies. RESULTS: The epidermal entrance echo thickness and thickness of dermis in males were higher than females, which was statistically significant on neck and dorsum of foot. The echo-density of dermis was higher in females on all sites, but was only statistically significant on neck. The epidermal entrance echo thickness and thickness of dermis in young age group was statistically higher than old group on sole and dorsal of the foot respectively. Overall, the skin thickness decreased with age. CONCLUSION: High frequency ultrasonography method provides a simple non-invasive method for evaluating the skin thickness and echo-density. Gender and age have significant effect on these parameters. Differences in study method, population, and body site likely account for different results previously reported.

To evaluate the cytotoxicity effects of luteolin (LUT) and kaempferol (KAE) via reactive oxygen species (ROS) mediated mitochondrial targeting on hepatocytes obtained from the liver of hepatocellular carcinoma (HCC) rats. In this study, HCC induced by diethylnitrosamine (DEN) and 2-acetylaminofluorene (2-AAF). In the following, rat liver hepatocytes and mitochondria were isolated and tested for every eventual apoptotic and anti-HCC effects of LUT and KAE. The results of MTT assay showed that LUT and KAE were able to induce selective cytotoxicity in hepatocytes of HCC group in a dose- and time-dependent manner. Treatment of mitochondria from hepatocytes of HCC group with LUT and KAE were accompanied by loss of mitochondrial membrane potential (MMP) and mitochondrial swelling and release of cytochrome c (P < 0.001) via reactive oxygen species (ROS) generation before cytotoxicity ensued. LUT and KAE also increased activation of caspase-3 (P < 0.001 and P < 0.01, respectively). Flow-cytometry analysis indicated that the mode of cell death induced by these flavonoids were mostly apoptosis. Importantly, LUT and KAE were nontoxic for healthy hepatocytes and mitochondria. Therefore, we suggest that LUT and KAE are a good candidate for the complementary therapeutic agent against HCC.

BACKGROUND: Investigations using a hybrid single photon emission computed tomography/computed tomography (SPECT-CT) scanning technique have been carried out in limited studies and have shown mixed results. However, the assessment of this technique for the detection of parathyroid adenoma in patients with a nodular goiter was performed in only one study with a small sample size. The aim of this prospective study was to assess the role of 99mTc-sestamibi parathyroid SPECT-CT scans for localization of parathyroid adenomas with a concomitant nodular goiter using 99mTc-methoxyisobutyl isonitrile (MIBI) scintigraphy and to compare it with SPECT and planar imaging. METHODS: This study was conducted on 48 patients with primary hyperparathyroidism and nodular goiter, who were candidates for parathyroid surgery and had been referred for parathyroid scintigraphy. The patients underwent an early set of planar 99mTc-MIBI scanning procedures first, followed by SPECT and CT scannings, and finally a delayed set of planar 99mTc-MIBI scannings. Sensitivity, specificity, negative and positive predictive values, and accuracy were determined on a per-parathyroid-gland basis for each scanning method, as defined by histology and follow-up. RESULTS: The surgery was successful in 48 out of 50 patients with primary hyperparathyroidism concomitant with thyroid nodularity, and data were completed for 80 sites in 48 patients. The accuracy of SPECT-CT in correctly identifying a parathyroid adenoma was 85.00, versus 75.00% for SPECT (P=0.01, significant). The sensitivity and specificity for SPECT-CT were 77.55 and 96.77%, respectively, versus 67.34 and 87.09%, respectively, for SPECT (P=0.12 and 0.12, not significant). There were nine sites that showed better localization on SPECT-CT scans relative to SPECT images, of which five sites were located in the ectopic regions. CONCLUSION: The results of our study indicate that SPECT-CT is more accurate than sestamibi planar imaging and SPECT for the preoperative identification of parathyroid lesions in patients with primary hyperparathyroidism concomitant with thyroid nodularity. Also, we would recommend the use of SPECT-CT for a workup of all patients with ectopic glands who are scheduled for minimally invasive parathyroid surgery.

OBJECTIVES: It has been suggested that obesity phenotypes are related to mental health problems and health-related quality of life (HRQoL). However, there is no certain consensus. This systematic review aimed to evaluate the association between different obesity phenotypes with common psychiatric symptoms and HRQoL. METHODS: Electronic databases i.e. PubMed, Scopus, EMBASE, and google scholar were searched until September 2021, to identify studies that investigated associations between the obesity phenotypes with psychiatric symptoms and/or mental and physical HRQoL. Two researchers independently checked titles and abstracts, evaluated full-text studies, extracted data, and appraised their quality using the Newcastle-Ottawa Scale. RESULTS: Eighteen studies, with a total of 3,929,203 participants, were included. Of the studies included in this systematic review, 10 articles evaluated the association between obesity phenotypes and psychiatric symptoms, while six papers investigated the association between HRQoL and obesity phenotypes, and two studies assessed both. As a whole, the findings of these studies suggest that obese individuals with a favorable metabolic profile have a slightly higher risk of mental health problems and poor quality of life, however, the risk becomes larger when obesity is combined with an adverse metabolic profile. So, metabolically healthy obesity may not be a completely benign condition in relation to mental disorders and poor quality of life. CONCLUSION: According to published research, obesity is likely to increase the risk of mental health problems and poor quality of life when metabolic disturbances are present.

Abstract Clinical trial studies revealed conflicting results on the effect of Ashwagandha extract on anxiety and stress. Therefore, we aimed to evaluate the effect of Ashwagandha supplementation on anxiety as well as stress. A systematic search was performed in PubMed/Medline, Scopus, and Google Scholar from inception until December 2021. We included randomized clinical trials (RCTs) that investigate the effect of Ashwagandha extract on anxiety and stress. The overall effect size was pooled by random‐effects model and the standardized mean difference (SMD) and 95% confidence interval (CIs) for outcomes were applied. Overall, 12 eligible papers with a total sample size of 1,002 participants and age range between 25 and 48 years were included in the current systematic review and meta‐analysis. We found that Ashwagandha supplementation significantly reduced anxiety (SMD: −1.55, 95% CI: −2.37, −0.74; p = .005; I 2 = 93.8%) and stress level (SMD: −1.75; 95% CI: −2.29, −1.22; p = .005; I 2 = 83.1%) compared to the placebo. Additionally, the non‐linear dose–response analysis indicated a favorable effect of Ashwagandha supplementation on anxiety until 12,000 mg/d and stress at dose of 300–600 mg/d. Finally, we identified that the certainty of the evidence was low for both outcomes. The current systematic review and dose–response meta‐analysis of RCTs revealed a beneficial effect in both stress and anxiety following Ashwagandha supplementation. However, further high‐quality studies are needed to firmly establish the clinical efficacy of the plant.

The response to methimazole [1-methyl-2-mercaptoimidazole (MMI)] therapy was evaluated in 18 patients with diffuse toxic goiter residing in an area of iodine deficiency (Tehran) and in 18 patients residing in an area of iodine sufficiency (Boston). The mean free T4 index (FT4I) decreased from 22.9 +/- 4.8 (+/- SD) to 4.9 +/- 4.3 in Tehran and from 23.8 +/- 5.2 to 17.0 +/- 4.1 in Boston after 4 weeks of MMI administration (10 mg, three times daily). The mean free T3 index (FT3I) decreased from 489 +/- 124 to 117 +/- 58 in Tehran and from 512 +/- 250 to 368 +/- 152 in Boston. In patients residing in Tehran, the FT4I was normal in 9 (less than 6.3 in 6), above normal in 1, and subnormal in 8 (44%) after 4 weeks of MMI treatment. In 4 of 8 patients with subnormal FT4I, serum TSH was also above normal, and clinical findings of hypothyroidism were evident. MMI (10 mg, twice daily) was then given to 15 additional patients with diffuse toxic goiter in Tehran. Mean FT4I values were 22.7 +/- 6.8, 12.1 +/- 2.5, 10.8 +/- 2.8, and 6.0 +/- 4.3 before and 8, 14, and 28 days after treatment, respectively. Corresponding mean FT3I values were 415 +/- 90, 196 +/- 36, 162 +/- 44, and 117 +/- 46. At 28 days, FT4I was subnormal in 7 (46%) patients, of whom 1 had increased TSH. These results indicate that treatment with recommended doses of MMI rapidly causes hypothyroidism in patients residing in Tehran, an area of iodine deficiency. Furthermore, they support the hypothesis that the dosage of thionamide compounds and the duration of therapy with the initial doses necessary to induce euthyroidism may vary in various parts of the world.

PURPOSE: To determine the prevalence of open-angle glaucoma (OAG), glaucoma suspects (GS), and ocular hypertension (OHT) in patients with thyroid-related immune orbitopathy (TRIO) and compare it with a control group. PATIENTS AND METHODS: In this cross-sectional analytic study, 233 eyes of 117 patients with TRIO (case group) and 240 eyes of 120 normal age and sex-matched individuals (control group) underwent complete ocular examinations. Grave orbitopathy (GO) was diagnosed by clinical examinations with the help of an endocrinologist and para clinic tests. Controls were selected among apparently healthy individuals with no history of previous orbitopathy or thyroid diseases. RESULTS: Prevalence of OAG and OHT was 2.5% and 8.5% in the case group, respectively. In contrast, OAG was detected in only 2 eyes (0.8%) of the control group and there were no instances of GS or OHT in the control group. Although the prevalence of OAG and GS were higher in cases than controls, this difference was not statistically significant. However, OHT was more common in cases (P<0.01). Ten eyes in the case group (4.3%) developed compressive optic neuropathy (CON); high intraocular pressure was detected in 5 of them (2.1%). All cases of OAG and GS in the case group were classified as stage 3 or higher of No symptoms or signs, Only signs no symptoms, Soft tissue, Proptosis, Extraocular muscle, Cornea, Sight loss. Active GO was only more prevalent in patients with OHT (P<0.001). CONCLUSIONS: The prevalence of OHT was higher in cases with GO than age and sex-matched controls. Ophthalmologic examinations including intraocular pressure measurement (and if needed automated visual fields) should be regularly performed in patients with GO particularly in higher stages and those with active disease.

In Brief Breast cancer is a devastating event for a woman. Physical changes and psychological problems, treatment to improve the patient's condition, and increased survival rates compared with other cancers manifest the importance of quality of life in these patients. This quality of life is affected by how the patients adjust to their situation. Hence, to understand adjustment to breast cancer, this research aimed to investigate the experience from the patients' perspective and how they interact with others and interpret their experiences in adjusting to the disease. A qualitative research approach based on grounded theory was used. The data were the result of 45 interviews with patients in different phases of their illness trajectory during 1 year, 6 interviews with families, and 10 observation sessions. The main categories that emerged were perceived threat to live, religious aspects, supportive dimensions, will to recover, increase in endurance, barriers to efforts leading to health, living with the disease with tolerance, and inhibitors and facilitators of tolerance. These main categories were understood as passages to reach evolutionary peaceful coexistence. Adjustment to breast cancer has positive evolutional process, and its direction is toward better adjustment. By positive mental reconstruction, the patients feel that they can live with their disease. Breast cancer is a devastating event for a woman. Physical changes and psychological problems, treatment to improve the patient's condition, and increased survival rates compared with other cancers manifest the importance of quality of life in these patients. This quality of life is affected by how the patients adjust to their situation. Hence, to understand adjustment to breast cancer, this research aimed to investigate the experience from the patients' perspective and how they interact with others and interpret their experiences in adjusting to the disease. A qualitative research approach based on grounded theory was used. The data were the result of 45 interviews with patients in different phases of their illness trajectory during 1 year, 6 interviews with families, and 10 observation sessions. The main categories that emerged were perceived threat to live, religious aspects, supportive dimensions, will to recover, increase in endurance, barriers to efforts leading to health, living with the disease with tolerance, and inhibitors and facilitators of tolerance. These main categories were understood as passages to reach evolutionary peaceful coexistence. Adjustment to breast cancer has positive evolutional process, and its direction is toward better adjustment. By positive mental reconstruction, the patients feel that they can live with their disease.

Dracocephalum kotschyi Boiss. (Labiatae) is a native Iranian medicinal plant which has been used in combination with Peganum harmala L. as a remedy for many forms of human cancer especially leukemia and gastrointestinal malignancies. Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. In this investigation HCC was induced by a single intraperitoneal injection of diethylnitrosamine (DEN) in corn oil at 200 mg/kg body weight to rats. Two weeks after DEN administration, cancer development was promoted with dietary 2-acetylaminofluorene (2-AAF) (0.02%, w/w) for 2 weeks. Serum alpha-fetoprotein (AFP) concentration, serum alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP) activities were also determined for confirmation of hepatocellular carcinoma induction. Then rat hepatocytes were isolated with collagen perfusion technique and tumoral hepatocytes were sorted by flow cytometry. Finally isolated mitochondria obtained from both tumoral and nontumoral hepatocytes were used for any probable toxic effect of Dracocephalum kotschyi ethanolic extract. Our results showed that D. kotschyi extract (250 µg/mL) induced reactive oxygen species (ROS) formation, mitochondrial membrane permeabilization (MMP), and mitochondrial swelling and cytochrome c release only in tumoral but not nontumoral hepatocyte. These findings propose Dracocephalum kotschyi as a promising candidate for future anticancer research.

Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death. In patients for whom HCC could not be detected early, current treatments show poor tolerance and low efficacy. So, alternative therapies with good efficacy are urgently needed. The aim of this research was to evaluate the selective apoptotic effects of myricetin (MYR), a flavonoid compound, on hepatocytes and mitochondria obtained from the liver of HCC rats. In this study, HCC induced by diethylnitrosamine (DEN), as an initiator, and 2-acetylaminofluorene (2-AAF), as a promoter. To confirm the HCC induction, serum levels of alpha-fetoprotein (AFP), AST, AST and ALP and histopathological changes in the liver tissue were evaluated. Rat liver hepatocytes and mitochondria for evaluation of the selective cytotoxic effects of MYR were isolated, and mitochondrial and cellular parameters related to apoptosis signalling were then determined. Our results showed that MYR was able to induce cytotoxicity only in hepatocytes from the HCC but not from the untreated control group. Besides, MYR (12.5, 25 and 50 μM) induced a considerable increase in reactive oxygen species (ROS) level, mitochondrial swelling, mitochondrial membrane permeabilization (MMP) and cytochrome c release only in cancerous but not in untreated normal hepatocyte mitochondria. MYR selectively increased caspase-3 activation and apoptotic phenotypes in HCC, but not untreated normal hepatocytes. Finally, our finding underlines MYR as a promising therapeutic candidate against HCC and recommends the compound for further studies.

BACKGROUND: Regional anesthesia is an alternative to general anesthesia in selected surgical settings. Paravertebral block as a regional anesthesia technique was compared with general anesthesia for elective breast surgeries regarding postoperative pain. MATERIAL/METHODS: Sixty patients scheduled for breast surgery were randomized to two groups of 30 patients each: general anesthesia (control group) and paravertebral block (study group). Postoperative pain, the primary outcome variable of the study, was assessed by a numeric rating scale at 1, 3, and 6 hours during the postoperative period. Total amount of morphine and hospital stay were also recorded. Student's t-test and ANOVA were used to compare results. A p value less than 0.05 was considered statistically significant. RESULTS: The paravertebral group was found to have better postoperative pain relief (p=0.0000), reduced need for morphine (p=0.0000), and a shorter hospital stay (p=0.0000) compared with the general anesthesia group. CONCLUSIONS: The study suggests paravertebral block as a suitable alternative to general anesthesia in selected breast surgical patients regarding postoperative pain reduction.

According to the divergent geographical distribution of the hepatitis C virus (HCV) and the fact that the virus possesses six major genotypes and more than 90 subtypes, we decided to determine the prevalence of the major HCV genotypes in the Islamic Republic of Iran. Serum samples from 21 HCV infected individuals were tested primarily by second generation of enzyme immunosorbent assay and the two-stage PCR method. For determining the five most common variants, second generation methods for genotype specification were used. The prevalence of specific genotypes in 15 samples is as follows: Type I/1a in seven cases, Type II/1b in three cases and Type V/3a in four patients. One sample disclosed Type 4.