The deleterious effects of cadmium on oxidative stress markers, drug-metabolizing, and antioxidant enzyme activities: Role of Silymarin and Garlic as Antioxidants.

Exposure to cadmium has been related to liver and kidney diseases such as polycystic and nephrotic syndrome. It is still unclear how cadmium contributes to these diseases. It is believed that the induction of oxidative stress resulting from the inhibition of antioxidant enzyme activities and changes in drug-metabolizing enzymes in the liver could explain the role of cadmium in the development of different diseases in the kidney and probably other organs. Changes in oxidative stress markers, antioxidant enzymes, and drug-metabolizing enzyme activities were assessed in the liver of male rats exposed to cadmium chloride. Additionally, the protective effects of silymarin and garlic extract against cadmium toxicosis were evaluated. Rats were randomly divided into eight groups as follows, groups 1, 2, 3, 4, and 5, received orally saline, CdCl2 (1 mg/kg), garlic extract [800 mg/kg], silymarin (25 mg/kg) and silymarin plus garlic extract respectively for 28 consecutive days. Rats in groups 6, 7, and 8 were pretreated with the same doses of garlic, silymarin, and garlic plus silymarin, respectively for two hours before cadmium administration. The Western immunoblotting technique was used to investigate the protein expression of cytochrome P450 isozymes. Spectrophotometric methods were used to assess the activity of both antioxidant- and drug-metabolizing enzymes. Free radical levels [measured as thiobarbituric acid reactive substances (TBARS)], catalase, superoxide dismutase, and glutathione peroxidase activities increased whereas the levels of glutathione and the activities of glutathione S-transferase, glutathione reductase, and glutamyl transferase, cytochrome P450, aryl hydrocarbon dehydrogenase (AHH), dimethylnitrosamine-N-demethylase I (DMN-dI), 7-ethoxycoumarine-O-deethylase (ECOD), cytochrome b5 and NADPH-Cytochrome-c-reductase enzyme activities decreased after cadmium treatment. Furthermore, Western immunoblotting data revealed that glutathione peroxidase protein expression increased following cadmium exposure, but cytochrome P450 2E1 and 3A4 expressions were downregulated. However, pretreatment of rats with silymarin or garlic extract or both before cadmium administration was found to restore the protein expression of cytochrome P450 2E1 and 3A4, the level of free radicals, antioxidant enzymes, drug-metabolizing enzyme activities to their normal levels. Similarly, histological studies revealed that silymarin and/or garlic extract reduced the liver damage caused by cadmium. Silymarin and/or garlic extract reduced the adverse effects of cadmium on the activity of both drug-metabolizing and antioxidant enzymes activity. These antioxidants could be provided to those who work in cadmium-based sectors to help them cope with the adverse effects of cadmium on their kidneys. In addition, Inhibiting drug-metabolizing enzyme activity should be considered when administering therapeutic medications to persons exposed to cadmium because most therapeutic drugs and many endogenous substances are largely metabolized by these enzymes.

Tramadol-induced hepato- and nephrotoxicity in rats: Role of Curcumin and Gallic acid as antioxidants.

Tramadol is an analgesic used to treat moderate to severe pain caused by cancer, osteoarthritis, and other musculoskeletal diseases. Cytochrome P450 system metabolizes tramadol and induces oxidative stress in different organs. Therefore, the present study aims at investigating the changes in the activities and the protein expressions of CYPs isozymes (2E1, 3A4, 2B1/2), antioxidants status, free radicals levels after pretreatment of rats with Curcumin and/or Gallic as single- and/or repeated-doses before administration of tramadol. In repeated-dose treatments of rats with tramadol, the activities of cytochrome P450, cytochrome b5, and NADPH-cytochrome-c-reductase, and the antioxidant enzymes including glutathione reductase, glutathione peroxidase, glutathione S-transferase, catalase, superoxide dismutase, and levels of glutathione were inhibited in the liver and the kidney of rats. Interestingly, such changes caused by tramadol restored to their normal levels after pretreatment of rats with either Curcumin and/or Gallic acid. On the other hand, repeated-dose treatment of rats with tramadol increased the activities of both dimethylnitrosamine N-demethylase I (DMN-dI), and aryl hydrocarbon hydroxylase (AHH) compared to the control group. However, pretreatment of rats with Curcumin and/or Gallic acid prior to administration of tramadol restored the inhibited DMN-dI activity and its protein expression (CYP 2E1) to their normal levels. On the other hand, tramadol inhibited the activity of ethoxycoumarin O-deethylase (ECOD) and suppressed its protein marker expression (CYP2B1/2), whereas Curcumin, Gallic acid and/or their mixture restored such changes to their normal levels. In conclusion, Curcumin and/or Gallic acid alleviated the adverse effects caused by tramadol. In addition, patients should be advice to take Curcumin and/or Gallic acid prior to tramadol treatment to alleviate the hepatic and renal toxicities caused by tramadol.

Robotic blue-dye sentinel lymph node detection for endometrial cancer - Factors predicting successful mapping.

OBJECTIVE: Sentinel lymph node (SLN) mapping has emerged as a viable option for the treatment of patients with endometrial cancer. We report our initial experience with SLN mapping algorithm, and examine the factors predicting successful SLN mapping. METHODS: We analyzed all data recorded in our institute on robotic blue-dye SLN detection mapping from the time it was first introduced to our department in January 2012-December 2014. Data included patient demographics, SLN allocation, operating room times, and pathology results. RESULTS: During the study period, 74 patients had robotic assisted surgery for endometrial cancer with attempted SLN mapping. SLN was found overall in 46 patients (62.1%). At first, SLN was detected in only 50% of cases, but after performing 30 cases, detection rates rose to 84.6% (OR = 3.34, CI 1.28-8.71; p = 0.003). Univariate analysis showed a higher detection rate with methylene blue than patent blue dye, 74.3% vs. 52.3% (OR = 2.744, 95% CI 1.026-7.344; p = 0.042). In multivariate analysis, high body mass index (BMI) was associated with failed mapping (OR = 0.899; 95% CI 0.808-1.00), as was the presence of lymph-vascular space invasion (LVSI) (OR = 0.126; 95% CI 0.24-0.658) and few cases per surgeon (OR = 1.083, 95% CI 1.032-1.118). Factors related to uterine pathology itself, including tumor histology, grade, method of diagnosis, the presence of an endometrial polyp, and lower uterine segment involvement were not found to be associated with successful mapping. CONCLUSIONS: Surgeon experience, BMI and LVSI may affect the success rate of SLN mapping for endometrial cancer. These factors should be investigated further in future studies.

Disrupted abdominal laparotomy wounds in gynaecologic oncology patients: benefits of active surgical re-closure.

OBJECTIVE: To assess the outcome of active management of disrupted wounds through surgical approximation and re-closure. METHOD: A prospective, non-comparative study, on all consecutive patients with disrupted laparotomy wounds treated at a tertiary medical centre, from November 2009 to December 2011. Data on patient demographics, diagnosis, type of abdominal incision, initial closure technique, infections and results of secondary re-closure were collected from the medical files. All patients underwent bedside closure with an en bloc mass suture mattress technique, performed by two attending gynaecologic oncologists. RESULTS: Of 197 patients who underwent abdominal laparotomy during the study period, 31 (16%) had a disrupted wound. Following surgical re-closure, 26 wounds (84%) were completely healed or needed only minor additional care by follow up on day 10. Five wounds (16%) failed primary management and required re-suturing; all subsequently healed. There were no long-term complications. CONCLUSION: Active surgical re-closure of disrupted abdominal laparotomy wounds is safe and effective in patients after treatment surgically for Müllerian malignancies.

Antioxidant activity of new aramide nanoparticles containing redox-active N-phthaloyl valine moieties in the hepatic cytochrome P450 system in male rats.

We report the synthesis of aramide nanoparticles containing a chiral N-phthaloyl valine moiety and their antioxidant activities on hepatic contents of cytochrome P450, amidopyrene N-demethylase, aniline-4-hyroxylase and induced the hepatic content of cytochrome b5 and nicotinamide adenine dinucleotide phosphate (NADPH) cytochrome C-reductase. Polymers were obtained as well-separated spherical nanoparticles while highly aggregated particles via H-bonding organization of the aramide-containing pyridine led to a thin layer formation. The effects of the nanoparticles and CCl4 on enzyme activities and thiobarbituric acid reactive substances (TBARS) levels of male rat liver were studied. Pretreatments of rats with the polyamides prior to the administration of CCl4 decreased the hepatic content of the tested enzymes. Doses reduced the toxic effects exerted by (•CCl3) upon the liver through inhibition of the cytochrome P450 system. Inhibition of such metabolizing enzymes could reduce the carcinogenic effects of chemical carcinogens.

Lindane-induced biochemical perturbations in rat serum and attenuation by omega-3 and Nigella sativa seed oil.

Lindane (gamma-hexachlorocyclohexane, gamma-HCH), a highly persistent organochlorine insecticide is neurotoxic at acute doses and has been reported to induce oxidative stress in cells and tissues. In this study, we investigated the antioxidant property of Nigella sativa seed oil (N.O) and omega-3 polyunsaturated fatty acids (omega3) against gamma-HCH-induced oxidative hepatic and renal damage in male rats serum. Rats were orally given sublethal dose of gamma-HCH (12 mg/kg, 24 h prior to decapitation), while N.O (0.3 ml/kg) and omega3 (20 mg/kg) were given every 48 h for 20 days single or together, or also combined with gamma-HCH. gamma-HCH caused a significant increase in the levels of serum total lipids, cholesterol, and triglycerides by 49, 61 and 30% respectively, while HDL-cholesterol decreased by 45% compared to control group. Pretreatment with omega3 and N.O prior gamma-HCH administration re-established the altered biochemical features and alleviated the harmful effects of gamma-HCH on lipid profile. The concentration of serum total protein and albumin was significantly decreased by 35 and 45% respectively in rats treated with gamma-HCH compared to control. gamma-HCH also caused hepatic and renal damage, as observed from the elevated serum levels of urea, creatinine, total bilirubin and uric acid contents and aminotransferases (AST and ALT), phosphatases (ACP and ALP) and lactate dehydrogenase (LDH) activities. Co-administration of omega3 and N.O reversed the hazardous effects induced by gamma-HCH on the liver and kidney and also protected acetylcholinesterase from the inhibitory action of gamma-HCH as well as suppressed the lipid peroxidation. Thus, the results show that omega3 and N.O might prevent oxidative stress and attenuate the changes in the biochemical parameters induced by gamma-HCH in male rats.

Sclerosing peritonitis associated with bilateral luteinized thecoma, linked to anticonvulsant therapy.

OBJECTIVE: To present a new case of sclerosing peritonitis associated with bilateral luteinized thecoma of the ovaries, linked to anticonvulsant therapy. CASE: A 22-year-old patient, receiving carbamazepine for seizures and anxiety attacks presented with shortness of breath, abdominal pain, nausea and vomiting. Clinical and imaging examinations revealed bilateral ovarian masses with massive ascites. At emergency surgery, bilateral ovarian luteinized thecoma with sclerosing peritonitis was found. Due to recurrent, postoperative episodes of small bowel obstruction she was treated with nasogastric suction, intravenous fluids and electrolyte replacement. Total parenteral nutrition was introduced. Since only partial improvement was achieved tamoxifen was administered with resolution of the bowel obstruction. CONCLUSIONS: This is the 19th case of sclerosing peritonitis associated with luteinized thecoma of the ovaries and the 3rd to be associated with anticonvulsant therapy. Treatment should be aimed at relief of bowel obstruction symptoms, preferably with conservative methods. Tamoxifen for downregulation of TGF-beta production should be considered as a treatment modality, as it proved to be very helpful in the presented patient.

Diazinon toxicity affects histophysiological and biochemical parameters in rabbits.

Diazinon is a widely used pesticide in agriculture. So, the current work aimed to investigate the effects of diazinon exposure on some physiological and biochemical parameters, as well as, histopathological changes and histochemical acetyl-cholinesterase activity (AChE). The red Baladi rabbits were dipped into water (Control Group), diazinon at low concentrations of 0.6 mg diazinon low concentration (DLC) or high concentration of 3mg diazinon high concentration (DHC) dissolved in 1l of water for 10s. Treatment was repeated after 10 days and animals were sacrificed between 0 and 21 days after the second treatment. Blood analysis revealed that Red blood cells (RBC's), hemoglobin (Hb) and plasma total protein (TP) were significantly decreased in both diazinon concentrations (P<0.01), (P<0.05), (P<0.01) respectively. Cholesterol and microsomal protein were increased (P<0.01), while, liver/ body weight and cytochrome P-450 were decreased in both concentrations (P<0.01). Also there was a highly significant effect of concentration X day interaction on all parameters (P<0.01). Histopathological changes of liver, kidney and brain were observed after DHC dipping. Glycogen content was decreased in liver and increased in kidney Bowman's capsule. Furthermore, AChE activity was inhibited in brain tissue, decreased in liver cells, but gradually increased in kidney glomerular cells. Therefore, kidney and brain were highly affected by diazinon exposure compared with the liver. Exposure of animals to diazinon caused extensive changes in physiological, biochemical, and histopathological parameters as well as histochemical AChE. So, contact exposure of diazinon leads to negative response on animal health.

BRCA susceptibility genes--a review of current conservative management of BRCA mutation carriers.

Three options for the management of a patient carrying a deleterious mutation in the BRCA gene exist: close surveillance, chemoprevention and prophylactic surgical procedures. We aimed at reviewing the current knowledge on the conservative management of patients who are found to be carriers of the BRCA susceptibility genes. Recent literature in the English language was reviewed for publications containing the conservative management of BRCA mutation-carriers. Close surveillance for the breasts includes breast self-examination, clinical examination by a specialist and breast imaging techniques--mammography and magnetic resonance imaging. Ovarian surveillance includes pelvic examination, transvaginal ultrasonography and blood CA-125 measurements. Age at beginning of examinations and their frequency are discussed. Chemoprevention includes tamoxifen and oral contraceptives for breast and ovarian cancer prevention, respectively.

Failure of sentinel node identification following neo-adjuvant chemo-radiotherapy for locally advanced squamous cell carcinoma of the vulva.

A case of a 70-year-old patient with advanced local vulvar cancer is presented. Treatment with neo-adjuvant chemo-radiotherapy for two courses was administered and two weeks after completion of treatment the patient underwent wide local excision with bilateral inguino-femoral lymph node dissection through three separate incisions. Two methods for the evaluation of sentinel nodes--lymphoscintigraphy and intraoperative gamma hand-held probe and blue dye injection, did not detect any sentinel node on either side. Groin-node dissection revealed 23 negative nodes. It is our hypothesis that the non-visualization of sentinel nodes in this patient was due to post-irradiation damage to the lymph channels.

The polymorphic CAG repeat in the androgen receptor gene in Jewish Israeli women with endometrial carcinoma.

BACKGROUND: Endometrial carcinoma is considered a hormonal-dependent tumor; estrogen induces endometrial cellular proliferation, whereas progestins display an antiproliferative effect on endometrial tissue. The role that androgen and its receptor (androgen receptor [AR]) play in the pathogenesis of endometrial carcinoma is less clear. Although androgen has an in vitro inhibitory effect on endometrial cell proliferation, up to 75% of endometrial carcinoma express AR somatically. A polymorphic CAG repeat within exon 1 of the AR encodes for a polyglutamine tract, with length range of 8 to 33 repeats, which is inversely correlated with the transcriptional activity of the AR. METHODS: To gain insight into the role of AR in endometrial carcinoma, the authors analyzed the polymorphic CAG repeat in 79 Jewish Israeli patients with endometrial carcinoma as compared with 44 healthy Jewish women serving as controls. Analysis was conducted using germline DNA as template and using polymerase chain reaction primers flanking the CAG repeat with subsequent fluorescent determination of allele sizes. RESULTS: Allele size range of the longer of the two alleles in the patients was 11-33 (mean, 19.8 +/- 2.7) and in the controls 10-22 (mean, 17.9 +/- 1.9), a statistically significant difference (P < 0.01). Allele size variation within the patient group did not correlate with disease stage, grade, reproductive history, or age at diagnosis. CONCLUSIONS: The authors conclude that AR-CAG repeat length differs in Jewish patients with endometrial carcinoma as compared with healthy individuals in Israel, and this finding increases the possibility that the AR is involved in the predisposition to this neoplasm.

The initial flare-up induced by gonadotropin releasing hormone agonist may serve as a predictor of ovarian response in the current IVF-ET treatment cycle in normogonadotropic women aged 40-48 years.

OBJECTIVE: Our purpose was to assess the potential role of the baseline hormone profile in combination with the initial pattern of response to gonadotropin releasing hormone (GnRH) analogue in predicting ovarian function and hence reproductive outcome in normogonadotropic patients aged 40 years or older undergoing IVF treatment. PATIENTS AND METHODS: A retrospective analysis of 394 controlled ovarian hyperstimulation (COH) cycles that reached the stage of oocyte retrieval was conducted. The study included 163 normogonadotropic (serum FSH < or = 15 IUIL) patients aged between 40 and 48 years who had regular menstrual cycles. Superovulation was achieved using menotropins in combination with GnRH analog (short protocol, beginning on menstrual day 2). The ovarian response was monitored on the third cycle day, the day following the first GnRH analogue administration. RESULTS: Cycle distribution by patient age was 175 (44.4%), 122 (30.9%), and 97 (24.7%), while the patient distribution was 85 (52.2%), 48 (29.5%), and 30 (18.3%) for age groups 40-41, 42-43, and 44-48 years, respectively. The mean total dose of menotropins needed for optimal COH was 1787 IU (range, 600-6000 IU). This dose increased with age, while the yield of oocytes and embryos declined (P < 0.05; ANOVA). A positive correlation was demonstrated between the E2 level on day 3 (GnRH analogue flare effect) and the outcome of the treatment cycle (number of oocytes and embryos). Using multiple stepwise regression analysis, it was demonstrated that the initial (day 3) serum E2 levels, combined with baseline FSH levels, patients's age and body mass index enabled early prediction of the ovarian response in the current IVF-ET treatment cycle (oocytes = 8.2 - 0.18 x Age + 0.17 x BMI - 0.12 x FSH + 0.0042 x E2). CONCLUSIONS: Multiple-parameter analysis demonstrated that the use of the initial E2 response to GnRH analogue stimulation combined with basic clinical data may assist in the prediction of ovarian function and hence the reproductive outcome in normogonadotropic IVF patients aged 40 years or older. This may serve as a clinical tool for improving patient selection and treatment outcome in IVF-ET.

Bacterial vaginosis in pregnancy treated with yoghurt.

As various drugs might have an effect on the fetus during pregnancy, the use of drugs should be minimized in the pregnant woman. Since bacterial vaginosis (BV) can be associated with prematurity and postpartum complications, we searched for alternative therapy for its cure during pregnancy. Commercial yoghurt incorporates both factors necessary for maintaining the protective mechanism of the vagina, vaginal pH and lactobacillus. A total of 32 women with BV in the first trimester of pregnancy were treated with intravaginal application of yoghurt. The result was favorable indicating that the continuous correction of vaginal pH and lactobacillus flora is crucial for normal vaginal ecology. During pregnancy, a local treatment restoring the normal acidity and vaginal flora, without systemic effect, may be preferable to any other treatment.