Potential Protective Role of Cyrtopodion Scabrum in Antioxidant Parameters in Serum and Liver of Rats with 5-FU-Induced Oxidative Damage.

Chemotherapy is the main approach for the treatment of cancer; however, it often causes unpleasant oxidative damages. Therefore, the development of an effective alternative/complementary therapy with improved tumor suppression efficiency and lower adverse effects is highly required. Recently, it has been shown that Cyrtopodion scabrum extract (CsE) is an effective and selective tumor suppressor medicine. The present study investigated the antioxidant activity of Cyrtopodion scabrum homogenate (CsH) and CsE and their effects on attenuating 5-fluorouracil (5-FU)-induced liver dysfunction in rats. A total of 60 male rats (weight: 200-220 g) were divided into six groups and treated for 14 days. The control (group I) and 5-FU (group II) groups received distilled water and 5-FU, respectively. The other four groups were orally administered with CsE, CsH, CsE+5-FU, and CsH+5-FU (groups III to VI), respectively by gavages based on a daily schedule. The 5-FU-induced oxidative damage was evaluated by changes in the weight and food and water intake during the treatment and antioxidant parameters in the liver and serum of the treated rats. The obtained data indicated that the administration of CsH and CsE significantly improved liver function and defense system of antioxidants by attenuating the levels or activities of malondialdehyde, superoxide anion, aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase and decrease of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione S-transferase, total antioxidant capacity, glutathione, total protein, and albumin in the liver and serum, induced by 5-FU treatment. The obtained data of the current study suggested that CsH and CsE play a protective role in the imbalance elicited by 5-FU and can be used as alternative/complementary supplements with 5-FU to reduce oxidative damages which is the consequence of reactive oxygen species production in cancerous patients.

Type 1 diabetes genetic risk score discriminates between monogenic and Type 1 diabetes in children diagnosed at the age of <5 years in the Iranian population.

AIM: To examine the extent to which discriminatory testing using antibodies and Type 1 diabetes genetic risk score, validated in European populations, is applicable in a non-European population. METHODS: We recruited 127 unrelated children with diabetes diagnosed between 9 months and 5 years from two centres in Iran. All children underwent targeted next-generation sequencing of 35 monogenic diabetes genes. We measured three islet autoantibodies (islet antigen 2, glutamic acid decarboxylase and zinc transporter 8) and generated a Type 1 diabetes genetic risk score in all children. RESULTS: We identified six children with monogenic diabetes, including four novel mutations: homozygous mutations in WFS1 (n=3), SLC19A2 and SLC29A3, and a heterozygous mutation in GCK. All clinical features were similar in children with monogenic diabetes (n=6) and in the rest of the cohort (n=121). The Type 1 diabetes genetic risk score discriminated children with monogenic from Type 1 diabetes [area under the receiver-operating characteristic curve 0.90 (95% CI 0.83-0.97)]. All children with monogenic diabetes were autoantibody-negative. In children with no mutation, 59 were positive to glutamic acid decarboxylase, 39 to islet antigen 2 and 31 to zinc transporter 8. Measuring zinc transporter 8 increased the number of autoantibody-positive individuals by eight. CONCLUSIONS: The present study provides the first evidence that Type 1 diabetes genetic risk score can be used to distinguish monogenic from Type 1 diabetes in an Iranian population with a large number of consanguineous unions. This test can be used to identify children with a higher probability of having monogenic diabetes who could then undergo genetic testing. Identification of these individuals would reduce the cost of treatment and improve the management of their clinical course.

The Effect of Oral Administration of Zinc Oxide Nanoparticles on Quantitative and Qualitative Properties of Arabic Ram Sperm and Some Antioxidant Parameters of Seminal Plasma in the Non-Breeding Season.

Zinc is an essential mineral and accepted as a trace element in the animal nutrition and for its role in biological enzymatic pathways. This study aimed to investigate the effect of oral administration of zinc oxide nanoparticles (ZnONPs) on some of the antioxidant parameters of semen plasma, quantitative and qualitative properties of Arabic ram sperm in the non-breeding season. Twelve adult Arabic rams (about 3-5 years old, 70 ±2.1 kg) were randomly assigned to receive one of the three levels of dietary ZnONPs (control; 0, group 1; 40 ppm and group 2; 80 ppm). Results showed that using different levels of ZnONPs increased the activity of superoxide dismutase enzyme (SOD) and total antioxidant capacity (TAC) of semen plasma significantly compared with the control group (P<0.05). Motility (74.83%), viability (76.90%), semen volume (1.76 ml) and sperm concentration (1418×106/ml) were significantly (P<0.05) higher in ZnONPs supplemented groups compared with the control group. The sperm morphological abnormalities reduced significantly in treated groups (10.46 and 9.07%) compared with the control group (12.66%; P <0.05). Also, the results suggested that 80 ppm level of ZnONPs increased the functionality of sperm membrane (44.38%) compared with other groups (37 and 35.66%, respectively for groups 1 and control) (P<0.05). Based on the results, using 80 ppm level of ZnONPs lead to an improvement in the activity of superoxide dismutase enzyme (48.62 ml) and total antioxidant capacity of semen plasma (111.88 µg/ml) compared with other groups (P<0.05). In conclusion using 80 ppm level of ZnONPs had a positive effect on the quantitative and qualitative properties of sperm and lead to a significant betterment in the activity of some antioxidant parameters of Arabic ram semen in the non-breeding season.

Post-transplantation Presentation of ANCA-associated Vasculitis: Granulomatosis with Polyangitis.

Granulomatosis with polyangitis (GPA) is characterized by necrotizing granulomatosis of the upper and lower respiratory tract and glomerulonephritis. If GPA does not respond to appropriate management, it might result in end-stage renal disease, which may remit the disease severity. The overall impression is that immunosuppression following renal transplantation would further subside the vasculitis. However, several studies have shown that systemic vasculitis recur in 25% of patients following renal transplantation. This may indicate the perplexing nature of the immune system. One of the key factors in prevention of relapse of GPA is following up of patients by careful immunosuppressive dose adjustment and regular measurement of biomarkers for vasculitis. Herein, we describe an interesting case of biopsy-proven GPA who had a complex long history of several post-transplantation relapses in different organs with anti-neutrophil cytoplasmic antibodies seroconversion. This case emphasizes that vasculitis in particular GPA can mimic various diseases depending on which vessels and organs are affected by the inflammation and is one of the reversible causes of failure of transplanted kidney. Bearing the diagnosis in mind as one of the potential differential diagnoses of failure of renal transplantation will lead to early diagnosis and treatment of recurrent GPA.

THE EFFECTS OF OPIUM ADDICTION ON THYROID AND SEX HORMONES IN DIABETIC AND NON-DIABETIC MALE AND FEMALE RATS.

OBJECTIVE: Opium is a narcotic drug that is commonly abused. The prescription of pharmaceutical derivatives of opium is limited due to their possible harmful effects on the body's metabolism and tolerability by patients. The aim of the present study was to evaluate the effects of chronic opium consumption on some sexual and thyroid hormones in diabetic and non-diabetic male and female rats. MATERIAL AND METHODS: This experimental study was conducted on 56 Wistar rats. The animals were divided into diabetic addicted (DA), diabetic non-addicted (DNA), non-diabetic addicted (NDA) and non-diabetic non-addicted (NDNA) groups of male and female rats. Peripheral blood samples were collected to measure the thyroid and sex hormone levels. Student's t-test was used to compare the mean values of the hormones between two groups. RESULTS: T3 serum level in male addicted groups significantly increased in comparison with non-addicted ones in both diabetic and non-diabetic groups. The testosterone level of male rats decreased due to the consumption of opium while it was significantly increased in diabetic and NDNA female rats in comparison with non-addicts. In DNA female animals, the mean level of 17-hydroxyprogesterone increased significantly compared with non-diabetic groups, however, it decreased in addicted females (diabetic and non-diabetic) in comparison with non-addicts. The level of DHEA-S increased significantly in diabetic and NDA male rats as compared with the non-addicted group. CONCLUSION: Opium affects the endocrine system in a sex-dependent manner, and opium could have different effects in diabetic and non-diabetic conditions.

Association of high dietary saturated fat intake and uncontrolled diabetes with constipation: evidence from the National Health and Nutrition Examination Survey.

BACKGROUND: Constipation is highly prevalent in the United States. The association of dietary fat intake with constipation has not been well studied. We recently reported that mice fed a high-fat diet had higher incidence of constipation than regular diet fed mice. The aim of this study was to assess if increased intake of dietary saturated fat in humans is also associated with higher risk of constipation and reduced stool frequency. METHODS: Analyses were based on data from 6207 adults (≥20 years) from the 2005-2006 and 2007-2008 cycles of the National Health and Nutrition Examination Surveys who had completed the bowel health questionnaire. Constipation was defined as a stool frequency of less than three times per week. Multivariable logistic regression analysis was used to calculate adjusted prevalence odds ratio (OR) estimates. Statistical analyses were performed using R and RStudio softwares. KEY RESULTS: The prevalence of constipation in this sample was 3.1%. After multivariable adjustment high saturated fat remained associated with constipation. The OR for high saturated fat intake associated with constipation was much higher in diabetics above 65 years, especially in non-Hispanic blacks, females, and those with poor glycemic control, compared to the control group. CONCLUSIONS & INFERENCES: To the best of our knowledge, this is the first report to investigate the association of high saturated fat diet, bowel frequency, and diabetes. This study demonstrates that a high dietary saturated fat intake is associated with significant increase in the prevalence of constipation, especially in the uncontrolled diabetic, non-Hispanic black, female patients.

A case of colon cancer with breast metastasis and krukenberg tumor.

UNLABELLED: Colorectal cancer most commonly metastasizes to the liver and lung. Metastatic colon carcinoma (MCC) to the breast is extremely rare. Krukenberg tumor is an uncommon metastatic tumor of the ovary. CASE PRESENTATION: A 38 years woman presented with abdominal pain. In evaluation colon cancer was diagnosed at stage 3. FOLFOX chemotherapy was done. After one year she developed Krukenberg tumor. Few days after ovarian tumor resection breast tumor was diagnosed. In immunohistochemistry both ovarian and breast tumors was CK7 negative, CK20 positive, compatible with colon cancer origin. This is the first case of simultaneous metastasis of colon cancer to two rare sites.

Alternate-day fasting diet improves fructose-induced insulin resistance in mice.

Increased fructose consumption is linked to insulin resistance, weight gain, hyperlipidemia and hypertension. Although the advantages of several dietary restriction regimens have been demonstrated, the effects of alternate-day fasting (ADF) on fructose-induced insulin resistance have not yet been studied. This study is based on a new modification on ADF by combining the fructose-rich solution (10% w/v) and regular mice diet. Mice were randomly allocated into four groups: ADF50% (50% restriction in chow food intake but ad libitum fructose drink), ADF100% (100% restriction for chow food but ad libitum fructose drink), control (ad libitum chow food intake plus tap water) and daily food and fructose (DFF) (had free access to both chow and fructose solution). Biweekly fasting blood sugar (FBS), glucose tolerance test (GTT) and insulin tolerance test (ITT) were conducted. All groups gained weight during the study (p < 0.05). Body weights of DFF and control groups did not differ from that of ADF groups, but ADF50% gained more (p < 0.01) weights than ADF100% through the study. Total calorie intake (feed + fast days) of ADF50% was higher than that of ADF100% (p < 0.001) and control (p < 0.03). In addition, ADF groups consumed more energy than the control and DFF groups in feed (ad libitum) days (p < 0.05). At the end of the study, the mean FBS levels in the control and ADF100% groups were similar and significantly lower in relation to that of DFF and ADF50% groups (p < 0.01). Measurements of area under the curve in GTT and ITT revealed that the ADF100% group was more insulin-sensitive than the DFF and ADF50% groups. In conclusion, these data suggest that the ADF100% improves fructose-induced insulin resistance in mice.

The interleukin-1 family gene polymorphisms and Graves' disease.

Genetic factors, including cytokine gene polymorphisms, are potential contributors to the pathogenesis of the Graves' disease (GD). We attempted in this study to determine the association between GD and the following polymorphisms in the interleukin-1 (IL-1) family genes: IL-1alpha (-889C/T), IL-1ss (-511C/T), IL-1ss (+3962C/T), IL-1R (Pst-1 1970C/T) and IL-1RA (Mspa-I 11100C/T). We studied 107 patients with an established diagnosis of GD and 140 healthy controls. Cytokine typing was performed by the polymerase chain reaction with sequence-specific primers assay. Genotype distributions among patients were in Hardy-Weinberg equilibrium for all polymorphisms. The frequency of the IL-1alpha -889T allele was significantly higher in patients than in controls (51.9% vs. 31.6%, OR=2.33, 95% CI=1.61-3.38; p<0.0001). The IL-1RA Msp-I 11100C allele was significantly more frequent in patients than in controls (50.0% vs. 22.9%, OR=3.38, 95% CI=2.29-4.97, p<0.0001). No significant associations were found for other polymorphisms. Although the IL-1 family has well-known roles in GD pathogenesis, the contributions of their genetic variations to the disease are unclear. In this study, we documented a highly significant association between GD and polymorphism in IL-1alpha and IL-1RA genes. Further studies in other populations are necessary to confirm our results.

Elevated expression levels of testis-specific genes TEX101 and SPATA19 in basal cell carcinoma and their correlation with clinical and pathological features.

BACKGROUND: Basal cell carcinoma (BCC) is characterized by a low rate of metastasis, slow growth and strong stroma dependency, with significant morbidity and public health burden. Cancer-testis (CT) genes are specifically expressed in normal testis, fetal ovary and different types of cancers. Testis immune privileged status makes CT genes promising candidates as cancer markers, vaccines and immunotherapy. OBJECTIVES: To find new CT genes as cancer markers and candidate genes for immunotherapy and to correlate pathological and clinical features with their expression in patients with BCC. METHODS: By means of digital differential display, seven testis-specific genes were selected. Their expression patterns were analysed in 78 BCC and 15 normal skin samples using semiquantitative reverse transcription-polymerase chain reaction. Pathological and clinical characteristics were determined using appropriate methods. RESULTS: SPATA19, TEX101, ODF1, ODF2 and ODF3 were expressed in 56.6%, 38.2%, 2.6%, 17.4% and 2.6% of BCCs but not in normal skin samples. ODF4 and PASD1 were not expressed in any BCC samples. TEX101 and SPATA19 expression in high-risk BCCs was higher than in low-risk tumours (P < 0.001). SPATA19 expression was correlated with a history of cancer radiotherapy (P < 0.001). Significant associations were found between expression of TEX101 with nodular subtype, ODF2 with infiltrating subtype, and ODF1 with tumours located on the neck. Among gene expressors, 42.1% co-expressed two genes and 5.3% co-expressed three genes. CONCLUSIONS: We report five new CT antigens, of which SPATA19 and TEX101 may be possible targets for cancer immunotherapy and novel markers for early detection of BCC.

Pleural fluid and serum eosinophilia: association with fluoxetine hydrochloride.

We report the case of a patient who was treated with fluoxetine hydrochloride (Prozac) for depression. Approximately 8 weeks into the treatment, an eosinophilic pleural effusion and serum eosinophilia developed. An extensive workup for the etiology of eosinophilic pleural effusion was unrevealing. Pleural biopsy showed a nonspecific inflammatory reaction and mild fibrosis. The pleural effusion and eosinophilia resolved within a few weeks of cessation of the drug. Fluoxetine can be associated with pleural and serum eosinophilia, possibly through an allergic-mediated reaction.

Neurosarcoidosis resembling meningioma: MRI characteristics and pathologic correlation.

A 37-year-old woman had visual changes. Magnetic resonance imaging showed an extraaxial mass in the anterior clinoid region that was presumed to be meningioma. There was no evidence of systemic or leptomeningeal disease. Pathologic findings were consistent with sarcoidosis. Isolated mass-like neurosarcoidosis, without systemic or leptomeningeal disease is difficult to diagnose preoperatively.

Aldose reductase induction: a novel response to oxidative stress of smooth muscle cells.

Hydrogen peroxide (H2O2) or 4-hydroxy-2,3-trans-nonenal (HNE) treatment of rat vascular smooth muscle cells (A7r5) caused induction of aldose reductase mRNA. Induction was dose (10-100 microM H2O2, 1-10 microM HNE) and time dependent, reaching a maximum (three- to fourfold) after 7-12 h. Treatment of cells with actinomycin D confirmed de novo synthesis of aldose reductase mRNA. H2O2-induced expression was prevented by catalase but unaffected by Desferal, indicating that metal catalyzed degradation of peroxide was not involved. Induction of enzymatically active aldose reductase by H2O2 and HNE was confirmed using Western blotting and enzyme assays. Aldose reductase can metabolize several aldehyde compounds including HNE, a major toxic product of lipid peroxidation. Inclusion of Sorbinil, an aldose reductase inhibitor, in toxicity assays resulted in a significant (twofold) enhancement of HNE-mediated killing of A7r5 cells, suggesting a protective role of aldose reductase against HNE-induced cell death. These data indicate that the induction of aldose reductase during oxidative stress might represent an important cellular antioxidant defense mechanism.

4-hydroxy-2,3-trans-nonenal induces transcription and expression of aldose reductase.

Treatment of A7r5 rat vascular smooth muscle cells with 4-hydroxy-2,3-trans-nonenal (HNE) resulted in increased aldose reductase mRNA transcription. Induction was time dependent, reaching a maximum (2,3-fold) after 7 hours. An enzymatically active aldose reductase analysed by Western blotting and enzyme assays was expressed. Sorbinil, an aldose reductase inhibitor, induced a significant enhancement of HNE cytotoxicity, indicating a protective role of aldose reductase against HNE-induced A7r5 cell death. These data indicate that induction of aldose reductase by HNE may represent an important cellular defence mechanism against oxidative injury.

Foreign body giant cell reaction associated with epidermoid tumor: CT and MR findings.

A patient with a known epidermoid tumor presented with a new large ring-enhancing mass adjacent to the cyst. Histopathology showed foreign body giant cell reaction adjacent to the epidermoid cyst. The CT and MR imaging appearances are described. The neuroimaging findings are identical to malignant degeneration to squamous cell carcinoma.

Intracytoplasmic lumina in meningioma: an ultrastructural and immunohistological study.

Three surgically removed meningotheliomatous meningiomas with hyaline inclusions or pseudopsammoma bodies were studied. Ultrastructurally, the lumina seemed to be predominantly intracytoplasmic, defined by a systemic unit membrane; they displayed abundant microvilli and contained granular or filamentous material, vacuoles, vesicular bodies, and lamellar structure. The cytoplasm surrounding the intracytoplasmic lumina was electron-dense and contained tonofilaments and desmosomal junctions. All three meningiomas showed expression of carcinoembryonic antigen, cytokeratin, and epithelial membrane antigen in the cells surrounding the hyaline bodies. Keratin, alpha-1-antitrypsin, and immunoglobulin M showed weak positive staining. There was widespread vimentin except in the cells with hyaline inclusions. Glial fibrillary acidic protein and S100 were negative. These results provide additional confirmation of immunohistochemical data that can serve as evidence for epithelial and secretory differentiation in meningiomas.

Fatal athletic injuries.

Death during athletic training or competition often brings public media attention. Recent endeavors to attract amateur athletic competitions to Marion County, Indiana prompted a review of athletic fatalities. Trauma during training, arteriosclerotic heart disease, and congenital heart defects cause most fatalities. A prospective study has been initiated to investigate and document these deaths.

Juvenile Alzheimer's disease with cerebellar involvement.

We describe a sporadic case of Alzheimer's disease with cerebellar involvement in a man, who died at age 32 years after an illness lasting seven years, which was marked by progressive dementia and ataxia. The brain was quite atrophic and showed numerous senile plaques of all types and neurofibrillary tangles in the cerebral cortex with some involvement of the basal ganglia and diencephalon. There was cerebellocortical atrophy with numerous large, kurulike plaques. In addition, widespread severe congophilic angiopathy was noted.