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Aflatoxin B1 (AFB1) is known to derange the hepatorenal system by redox, DNA adduct formation and apoptotic networks. Endogenous 3‐indole propionic acid (3‐IPA) is a metabolite of tryptophan metabolism by gut microbiota that can protect against redox imbalance, inflammation and cellular lipid damage. We investigated the beneficial effect of 3‐IPA against AFB1‐mediated organ toxicity in male rats post 28 days of consecutive treatment. The 3‐IPA (25 and 50 mg/kg) was orally administered alongside AFB1 (50 μg/kg) treatment. Biochemical and enzyme‐linked immunosorbent assays were utilised to examine biomarkers of hepatorenal function, oxidative status and inflammation. DNA damage and apoptosis were also assessed, and histological staining techniques were used to investigate hepatorenal tissues for pathological indicators. The 3‐IPA supplementation abated AFB1‐mediated increases in biomarkers of hepatic and renal dysfunction in rat serum. Co‐administration of 3‐IPA further reduced AFB1‐induced redox imbalance (by upregulating antioxidant mediators and enzymes [GSH, TSH, Trx, Trx‐R, SOD, CAT, GPx and GST]; reducing reactive oxygen species, lipid peroxidation and DNA adduct [RONS, LPO and 8‐OH‐dG] formation; suppressing pro‐inflammatory and apoptotic mediators [XO, MPO, NO, IL‐1β and Casp −9 and −3]; and upregulating the level of interleukin 10 (IL‐10). Moreover, treatment with 3‐IPA lessened hepatorenal tissue injuries. These findings suggest that augmenting 3‐IPA endogenously from tryptophan metabolism may provide a novel strategy to forestall xenobiotics‐mediated hepatorenal toxicity, including AFB1. [ABSTRACT FROM AUTHOR]

Doxorubicin (DOX) is a chemotherapeutic drug used in the treatment of various cancer types. DOX toxic side effects include neuronopathy and memory deficits. We investigated the effect of the antioxidant luteolin (LUT: 50 or 100 mg/kg; per os) on DOX (2 mg/kg; intraperitoneal)‐induced oxidative stress (OS), inflammation, and apoptosis in the brain of Wistar rats for 14 days. We observed that LUT reduced DOX‐mediated increase in OS biomarkers—catalase, superoxide dismutase, glutathione‐S‐transferase, and glutathione peroxidase. LUT increased glutathione and total sulphydryl levels and alleviated DOX‐induced increases in the levels of reactive oxygen and nitrogen species, lipid peroxidation, myeloperoxidase, nitric oxide, tumor necrosis factor‐α, and interleukin‐1β (IL‐1β). Additionally, LUT suppressed caspase‐3 activity, increased anti‐inflammatory cytokine—IL‐10 level, and reduced pathological lesions in the examined organs of rats cotreated with LUT and DOX. Collectively, cotreatment with LUT lessened DOX‐induced neurotoxicity. Supplementation of LUT as a chemopreventive agent might be useful in patients undergoing DOX chemotherapy. [ABSTRACT FROM AUTHOR]

As gallic acid (GA) role in zearalenone (ZEN); mediated reproductive dysfunction has not been studied, we report on GA's effect on reproductive dysfunction in rats treated with ZEN‐100 µg/kg alone, or with GA‐40 mg/kg; for 4 weeks. The mycotoxin ZEN contaminates crops, causing toxicity on ingestion, economic losses, and alters reproductive function. Relative to control, GA reversed ZEN‐induced reduction of rats' testicular function enzymes and reproductive hormones and improved ZEN‐impaired sperm quality. GA significantly (p < 0.05) increased rats antioxidant status, inhibited (p < 0.05) reactive oxygen and nitrogen species and lipid peroxidation levels, and abated (p < 0.05) proinflammatory biomarkers in the examined organs: hypothalamus, testis, and epididymis. Histopathology revealed that GA facilitated the preservation of testicular and epididymal cytoarchitecture significantly altered in rat cohorts treated with ZEN alone. Conclusively, GA protected against ZEN‐induced toxicity in the rats' organs examined, enhanced endogenous antioxidative protective mechanism, and abated proinflammatory responses. GA further averted a decline in circulatory, reproductive enzymes, hormone levels. GA also protected against reproductive tissue damage and improved parameters of sperm functionality. [ABSTRACT FROM AUTHOR]

Perfluorooctanoic acid is a synthetic perfluoroalkyl—persistent in the environment and toxic to humans. N‐acetylcysteine is a pro‐drug of both amino acid l‐cysteine and glutathione—a non‐enzymatic antioxidant. N‐acetylcysteine serves as an antidote for paracetamol poisoning and alleviates cellular oxidative and inflammatory stressors. We investigated N‐acetylcysteine role against reproductive toxicity in male Wistar rats (weight: 140–220 g; 10 weeks old) posed by perfluorooctanoic acid exposure. Randomised rat cohorts were dosed both with perfluorooctanoic acid (5 mg/kg; p.o) or co‐dosed with N‐acetylcysteine (25 and 50 mg/kg p.o) for 28 days. Sperm physiognomies, biomarkers of testicular function and reproductive hormones, oxidative stress and inflammation were evaluated. Co‐treatment with N‐acetylcysteine significantly (p <.05) reversed perfluorooctanoic acid‐mediated decreases in reproductive enzyme activities, and adverse effect on testosterone, luteinising and follicle‐stimulating hormone concentrations. N‐acetylcysteine treatment alone, improved sperm motility, count and viability, and reduced total sperm abnormalities. Co‐treatment with N‐acetylcysteine mitigated perfluorooctanoic acid‐induced alterations in sperm function parameters. N‐acetylcysteine abated (p <.05) perfluorooctanoic acid‐induced oxidative stress in experimental rats testes and epididymis, and generally improved antioxidant enzyme activities and cellular thiol levels. Furthermore, N‐acetylcysteine suppressed inflammatory responses and remedied perfluorooctanoic acid‐mediated histological injuries in rat. Cooperatively, N‐acetylcysteine enhanced reproductive function in perfluorooctanoic acid dosed rats, by lessening oxidative and nitrative stressors and mitigated inflammatory responses in the examined organ. [ABSTRACT FROM AUTHOR]

The neurotoxic impact of dietary exposure to aflatoxin B1 (AFB1) is documented in experimental and epidemiological studies. Gallic acid (GA) is a triphenolic phytochemical with potent anticancer, anti‐inflammatory, and antioxidant activities. There is a knowledge gap on the influence of GA on AFB1‐induced neurotoxicity. This study probed the influence of GA on neurobehavioral and biochemical abnormalities in rats orally treated with AFB1 per se (75 µg/kg body weight) or administered together with GA (20 and 40 mg/kg) for 28 uninterrupted days. Behavioral endpoints obtained with video‐tracking software demonstrated significant (p <.05) abatement of AFB1‐induced anxiogenic‐like behaviors (increased freezing, urination, and fecal bolus discharge), motor and locomotor inadequacies, namely increased negative geotaxis and diminished grip strength, absolute turn angle, total time mobile, body rotation, maximum speed, and total distance traveled by GA. The improvement of exploratory behavior in animals that received both AFB1 and GA was confirmed by track plots and heat maps appraisal. Abatement of AFB1‐induced decreases in acetylcholinesterase activity, antioxidant status and glutathione level by GA was accompanied by a marked reduction in oxidative stress markers in the cerebellum and cerebrum of rats. Additionally, GA treatment abrogated AFB1‐mediated decrease in interleukin‐10 and elevation of inflammatory indices, namely tumor necrosis factor‐α, myeloperoxidase activity, interleukin‐1β, and nitric oxide. Further, GA treatment curtailed caspase‐3 activation and histological injuries in the cerebral and cerebellar tissues. In conclusion, abatement of AFB1‐induced neurobehavioral abnormalities by GA involves anti‐inflammatory, antioxidant, and antiapoptotic mechanisms in rats. [ABSTRACT FROM AUTHOR]

Petroleum products—petrol, kerosene, and diesel—composed of volatile organic constituents contribute to air pollution. Exposure of gas station attendants (GSAs) to petroleum products fumes (PPFs) may account for occupation‐related predisposition to respiratory toxicity and disease pathogenesis. We simulated GSA exposure to PPF inhalation and examined their effect on oxido‐inflammatory responses, toxicity, and histopathological alterations in rat lungs, following 8‐hours daily exposure for 60 and 90 days. Reactive oxygen and nitrogen species (RONS), oxidative stress and inflammatory biomarkers, namely: superoxide dismutase (SOD), reduced glutathione (GSH), glutathione peroxidase (GPx), glutathione‐S‐transferase (GST), TNF‐α, IL‐1β, xanthine oxidase (XO), nitric oxide (NO) activity were evaluated. Besides, histopathological examination of the lungs and trachea of exposed rats, PPF exposure resulted in significant (P <.05) increases in RONS, biomarkers of oxidative stress, pro‐inflammation cytokines, and reduced (P <.05) GSH levels in rats, secondary to histopathological alteration in lungs and trachea cytoarchitecture examined in an exposure‐duration‐dependent manner. We conclude, therefore, that the observed biochemical and histological changes create a microenvironment that is permissive to diseases pathogenesis of the respiratory system via oxido‐inflammatory mechanistic pathways. [ABSTRACT FROM AUTHOR]

The increase in the exposure to carbon nanotubes (CNTs) and their incorporation into industrial, electronic, and biomedical products have required several scientific investigations into the toxicity associated with CNTs. Studies have shown that the metabolism and clearance of multiwalled CNTs (MWCNTs) from the body involve biotransformation in the liver and its excretion via the kidney. Since oxidative stress and inflammation underlines the toxicity of MWCNT, we investigated the ameliorative effect of kolaviron (KV), a natural antioxidant and anti‐inflammatory agent, on hepatorenal damage in rats. Exposure to MWCNTs for 15 days significantly increased serum activities of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and lactate dehydrogenase thereby suggesting hepatic dysfunction. Kidney function, which was monitored by urea and creatinine levels, was also impaired by MWCNTs. Additionally, MWCNTs markedly increased myeloperoxidase activity, nitric oxide level, reactive oxygen and nitrogen species, and tumor necrosis factor level in both tissues. However, KV in a dose‐dependent manner markedly attenuated MWCNT‐induced markers of hepatorenal function in the serum and MWCNT‐associated inflammation in the liver and kidney. Also, MWCNTs elicited significant inhibition of superoxide dismutase, catalase, glutathione peroxidase, and glutathione‐S‐transferase activities. There was a significant diminution in glutathione level (GSH) and enhanced production of malondialdehyde (MDA) in MWCNTs‐exposed rats. KV treatment was able to significantly increase the antioxidant enzymes and enhance the GSH level with a subsequent reduction in the MDA level. Taken together, KV elicited ameliorative effects against hepatorenal damage via its anti‐inflammatory and antioxidant properties. Thus, KV could be an important intervention strategy for the hepatorenal damage associated with MWCNTs exposure. [ABSTRACT FROM AUTHOR]

Excessive exposure to Copper (Cu) may result in Cu toxicity and adversely affect health outcomes. We investigated the protective role of rutin on Cu‐induced brain damage. Experimental rats were treated as follows: group I: control; group II: Cu‐sulfate: 200 mg/kg; group III: Cu‐sulfate, and rutin 100 mg/kg; and group IV: rutin 100 mg/kg, for 7 weeks. Cu only treatment significantly decreased body weight gain, while rutin cotreatment reversed this decrease. Cu treatment increased malondialdehyde, nitric oxide level, and myeloperoxidase activity and decreased superoxide dismutase and catalase activities in rat brain. Immunohistochemistry showed that COX‐2, iNOS, and Bcl‐2 proteins were strongly expressed, while Bax was mildly expressed in the brain of Cu‐treated rats. Furthermore, brain histology revealed degenerated neurons, and perforated laminae of cerebral cortex in the Cu‐only treated rats. Interestingly, coadministration of Cu and rutin reduced the observed histological alteration, improved inflammatory and antioxidant biomarkers, thereby protecting against Cu‐induced brain damage via antioxidative and anti‐inflammatory mechanisms. [ABSTRACT FROM AUTHOR]

The adverse effect of diclofenac administration on the male reproductive organ in both humans and rats has been reported. Selenium, a trace element vital in nutrition, plays a significant part in cellular redox homeostasis, including male reproduction. However, the impact of selenium on male reproductive toxicity associated with diclofenac administration is lacking in the literature. The current investigation assessed the modulatory effects of selenium on diclofenac‐mediated reproductive toxicity in rats. Rats were treated for fourteen consecutive days, either with diclofenac (10 mg/kg) or co‐treated with selenium (0.125 and 0.25 mg/kg) body weight. Sperm parameters, enzymes of testicular function, luteinizing, follicle‐stimulating hormone and testosterone were assessed in addition to oxidative stress indices and histopathological changes. Selenium significantly alleviated diclofenac‐induced decreases in sperm count and motility, testicular function enzymes and levels of luteinizing hormone and testosterone in serum. Moreover, selenium co‐administration at 0.125 and 0.25 mg/kg inhibited the diclofenac‐induced decrease of antioxidant enzyme activities and increased oxidative stress parameters—lipid peroxidation, reactive nitrogen and oxygen species—in epididymis and testes of rats. Selenium (0.25 mg/kg) alone ameliorated diclofenac‐mediated histological injuries in exposed rats. Collectively, selenium enhanced testicular and epididymal function in diclofenac‐treated rats by suppressing nitrosative and oxidative stress in rats. [ABSTRACT FROM AUTHOR]

Environmental contamination by manganese is correlated with diverse health outcomes plus reproductive dysfunction. Dietary gallic acid (GA) and omega‐3 fatty acids (ω‐3‐FA) are well reported to elicit beneficial health effects. Though, information on GA and ω‐3‐FA effects on manganese‐induced reproductive toxicity is absent in literature. We examined the effect of GA or ω‐3‐FA on manganese‐induced epididymal and testicular toxicity in rats, exposed to manganese (15 mg/kg b.w.) alone, in combination with GA (30 mg/kg b.w.) or ω‐3‐FA (20 mg/kg b.w.) by gavage for 14 consecutive days. GA or ω‐3‐FA significantly (p <.05) prevented manganese‐mediated increase in lipid peroxidation, myeloperoxidase activity, reactive oxygen and nitrogen species production but increased antioxidant enzymes activities and glutathione level in epididymis and testes treated rats. GA or ω‐3‐FA enhanced the activities of testicular function marker enzymes, namely acid phosphatase (ACP), lactate dehydrogenase (LDH), alkaline phosphatase (ALP) and glucose‐6‐phosphate dehydrogenase (G6PD) in the treated rats. GA or ω‐3‐FA amelioration of manganese‐induced decreases in follicle‐stimulating hormone, luteinising hormone, and testosterone levels were complemented by increase (p <.05) sperm functional characteristics in treated rats. Conclusively, GA or ω‐3‐FA may serve as dietary supplements to improve male reproductive dysfunction associated with manganese toxicity. [ABSTRACT FROM AUTHOR]

Protocatechuic acid (PA) is a polyphenol—recognized for its efficacy as an antioxidant—possesses anticancer, anti‐inflammatory, antioxidant properties. The efficacy of PA in the management of benign prostatic hyperplasia (BPH) has not been investigated. Forty‐two castrated rats (n = 7) were treated as follows: control (corn oil), BPH only received testosterone propionate (TP) (TP 3 mg/kg intraperitoneally), BPH + PA (TP 3 mg/kg + PA 40 mg/kg), BPH + finasteride (Fin) (TP 3 mg/kg + Fin 10 mg/kg), PA only (40 mg/kg: by gavage), and Fin only (10 mg/kg: by gavage) for 4 weeks. In BPH rats, there were significant (P <.05) increases in prostatic (250%) and organosomatic (280%) weights compared with controls. Cotreatment decreased prostatic weights by 19% (PA) and 21% (Fin). Markers of inflammation: myeloperoxidase activities increased in serum (148%) and prostate (70%), as well as nitric oxide levels serum (92%) and prostatic (95%). Proinflammatory cytokines interleukin‐1β and tumor necrosis factor‐α increased by 3.6‐ and 2.8‐fold. Furthermore, prostatic malondialdehyde, superoxide dismutase, and serum total acid phosphatase increased by 97%, 25%, and 48%, respectively. Histology revealed poor architecture and severe proliferation of the prostate in BPH rats. Inflammation and oxidative stress markers, as well as the histological alteration in BPH rats, was attenuated (P <.05) upon cotreatment with PA and comparable with Fin cotreatment. These results suggest that PA mitigates oxido‐inflammatory responses and restored prostatic cytoarchitecture to levels comparable with control in rats induced with BPH. [ABSTRACT FROM AUTHOR]

The present study examined the influence of co‐exposure to cadmium (Cd) and nickel (Ni) on hepatorenal function as well as the protective role of omega‐3 polyunsaturated fatty acids (ω‐3FA) in rats. The animals were exposed to Cd (5 mg/kg) and Ni (150 μg/L in drinking water) singly or co‐exposed to both metals and ω‐3FA at 20 mg/kg for 14 consecutive days. Results showed that hepatorenal injury resulting from individual exposure to Cd or Ni was not aggravated in the co‐exposure group. Moreover, ω‐3FA markedly abrogated the reduction in the antioxidant enzyme activities, the increase in reactive oxygen and nitrogen species, and lipid peroxidation induced by Cd and Ni co‐exposure. Additionally, ω‐3FA administration markedly suppressed the increase in hepatic and renal myeloperoxidase activity, nitric oxide, tumor necrosis factor alpha, and interleukin‐1 β levels in the co‐exposure group. Genotoxicity resulting from individual exposure to Cd or Ni was intensified in the co‐exposure group. However, ω‐3FA administration markedly ameliorated the genotoxicity and histological lesions in the co‐exposure group. Taken together, co‐exposure to Cd and Ni aggravated genotoxicity and not oxido‐inflammatory stress in the liver and kidney of rats. ω‐3FA abated hepatorenal injury and genotoxicity induced by Cd and Ni co‐exposure in rats. [ABSTRACT FROM AUTHOR]

Aim: Data on the changing levels in renal morbidity and mortality are scant globally. We sought to assess trends in renal disease mortality and attributable causes over a 20 year period in Ghana. Methods: A retrospective analysis of 20 year autopsy records of the Pathology Departments of leading teaching hospitals in Ghana, (Korle‐Bu Teaching Hospital (KBTH) in Accra and Komfo Anokye Teaching Hospital (KATH) in Kumasi) from January 1994 to December 2013. Data comprising autopsies from in‐patients, community cases and coroners' cases were used. We defined primary cause of death as death directly due to renal disease and secondary cause of death as death in which renal disease was a comorbid or contributing factor. Results: Over the period, there were a total of 94 309 deaths, of which 5608 were attributed to renal disease (5.9/100). Mortality rate remained fairly the same from 1994 to 2009 (5.0%), but doubled from 2010 to 2013 (10.8%). Similar trends were observed among males and females during the same period. However, males had slightly higher mortality rates (6.6%; 95% CI: 46.1%–6.8%) compared to females (5.6%; 95% CI: 5.4%–5.8%; P = 0.271). The major leading attributable causes of renal disease death include end stage renal disease 45.0% and acute pyelonephritis accounting for 20.9% of the cases. Hypertensive heart disease accounted for 30.0% of all secondary cause of death while congestive heart disease and septicaemia accounted for 13.0% and 12.0%, respectively. Conclusions: We observed marked increase in the renal disease mortality rate during the last few years predominantly driven by chronic and infectious related renal diseases as a main cause, and hypertensive heart disease and congestive heart failure as the main secondary causes. Measures geared towards prevention, treatment and managing such conditions may impact on the reduction of renal disease mortality rate among Ghanaian populations. Summary at a Glance: A retrospective analysis of 20 year autopsy records of the Pathology Departments of leading teaching hospitals in Ghana, to identify the contribution of renal disease as a cause of death. 5.9% of all deaths were attributed to renal causes. Mortality rates attributed to renal disease had increased from 5.0% in the 1990s to 10.8% over the past 3 years. [ABSTRACT FROM AUTHOR]

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ABSTRACT Chemotherapy remains an important approach in the fight against malaria. Artemether-lumefantrine combination is widely in use due to its effectiveness against Plasmodium falciparum. Misuse in the form of multiple repeated doses of this anti-malaria drug is rampant in Nigeria. This study was designed to assess the hepatotoxic and clastogenic potential of extreme misuse of artemether-lumefantrine in rats. Graded doses of artemether-lumefantrine (1-5 mg/kg body weight) were administered by oral gavage for 6 weeks, twice daily, for 3 consecutive days per week. Artemether-lumefantrine, at all doses, did not have significant effects on the body and relative liver weight of treated group compared to the negative control group. The mean γ-glutamyltransferase, alanine, and aspartate aminotransaminase activity in groups of artemether-lumefantrine treated rats were significantly higher ( p < 0.05) than that of the negative control group indicating that repeated administration of artemether-lumefantrine may be hepatotoxic. Findings from histological analyses of liver cross-section support the enzyme pattern of hepatoxicity. In addition, the drug, at all experimental doses, significantly induced ( p < 0.05) formation of micronucleated polychromatic erythrocytes in the bone marrow cells of the treated rats compared with the negative control indicating clastogenic potential of the drug when misused. © 2013 Wiley Periodicals, Inc. Environ Toxicol 30: 301-307, 2015. [ABSTRACT FROM AUTHOR]

Kupffer cells (KCs) are important in hepatic homeostasis and responses to xenobiotics. KCs are activated on interaction with endotoxin, releasing cytokines, and reactive oxygen species normally associated with increased gene expression, cellular growth, or hepatic injury. Ethanol-induced endotoxemia is one means of KC activation. We propose that KC depletion attenuates the effect of EtOH-induced endotoxemia to impact the hepatic growth response. Hepatic DNA synthesis was examined in KC competent (KC+) or KC-depleted (KC−) C57BL/6 mice fed EtOH-containing diet in the presence or absence of polyphenol-60 antioxidant. KC depletion was assessed by F4/80 antigen, and DNA synthesis was assessed by 5-bromo-2′-deoxyuridine incorporation. Tumor necrosis factor alpha (TNF-α) messenger RNA released was quantified by RT-PCR/electrophoresis. ERK1/2 phosphorylation was evaluated by Western blotting, and Nrf2 and CYP2E1protein were also assayed. Apoptosis and hepatic injury were examined by the Tunnel assay and hepatic transaminases in serum, respectively. Hepatic transaminases in serum (AST and ALT) were within normal range. Over 90% of KC was depleted by clodronate treatment. KC depletion decreased TNF-α mRNA release, ERK1/2 phosphorylation, and hepatocyte DNA synthesis. KC depletion is associated with increased numbers of apoptotic cells bodies in KC− mice. Antioxidant treatment decreased DNA synthesis, Nrf2, and CYP2E1 protein expression in EtOH-consuming mice. Our data indicate that upon ethanol exposure, KC participates in hepatic DNA synthesis and growth responses. Collectively, these observations suggest that KC depletion attenuates the downstream effect of ethanol-induced endotoxemia by reduced cytokine and reactive oxygen species production with its concomitant effect on MAPK-signaling pathway on hepatocyte DNA synthesis. © 2012 Wiley Periodicals, Inc. Environ Toxicol 29: 867-875, 2014 [ABSTRACT FROM AUTHOR]

Background: The study of breast cancer in women with African ancestry offers the promise of identifying markers for risk assessment and treatment of triple-negative disease.Methods: African American and white American women with invasive cancer diagnosed at the Henry Ford Health System comprised the primary study population, and Ghanaian patients diagnosed and/or treated at the Komfo Anokye Teaching Hospital in Kumasi, Ghana constituted the comparison group. Formalin-fixed, paraffin-embedded specimens were transported to the University of Michigan for histopathology confirmation, and assessment of estrogen and progesterone receptors and HER-2/neu expression.Results: The study population included 1008 white Americans, 581 African Americans, and 75 Ghanaians. Mean age at diagnosis was 48.0 years for Ghanaian, 60.8 years for African American, and 62.4 for white American cases (P=.002). Proportions of Ghanaian, African American, and white American cases with estrogen receptor-negative tumors were 76%, 36%, and 22%, respectively (P<.001), and proportions with triple-negative disease were 82%, 26%, and 16%, respectively (P<.001). All Ghanaian cases were palpable, locally advanced cancers; 57 (76%) were grade 3. A total of 147 American women were diagnosed as stage III or IV; of these, 67.5% (n=46) of African Americans and 44.6% (n=29) of white Americans were grade 3. Among palpable, grade 3 cancers, Ghanaians had the highest prevalence of triple-negative tumors (82.2%), followed by African Americans (32.8%) and white Americans (10.2%).Conclusions: Our study demonstrates progressively increasing frequency of estrogen receptor-negative and triple-negative tumors among breast cancer patients with white American, African American, and Ghanaian/African backgrounds. This pattern indicates a need for additional investigations correlating the extent of African ancestry and high-risk breast cancer subtypes. [ABSTRACT FROM AUTHOR]

The article presents a study that addressed the potential of N-terminal BRCA1 peptide to block the immunoreactivity of endogeneous protein detected by the MS110 antibody in immunoblots and immunochemistry. The study also tested the ability of the peptide to block the detection pattern in formalin-fixed paraffin-embedded tissue. It notes the specificity of the MS110 antibody to BRCA1 as well as cites the factors causing the loss of MS110 immunoreactivity in familial BRCA1-associated tumours.

Field JW, Gutmann JL, Solomon ES, Rakusin H. A clinical radiographic retrospective assessment of the success rate of single-visit root canal treatment. International Endodontic Journal, 37, 70–82, 2004. To determine retrospectively the clinical and radiographic success rate of single-visit root canal treatment performed in a busy endodontic practice using contemporary techniques of canal cleaning, shaping and obturation. Seven hundred and sixty-eight single-visit cases, of which 223 presented for a re-examination appointment ranging from 6 months to 4 years from the day of treatment, were considered. Four endodontists provided examinations for both root canal treatment and re-examinations. Clinical and radiographic data were used to form an overall impression of the outcomes for each case at the time of re-examination. Available demographics and treatment information of these 223 cases were compiled for comparison. The number of treatment visits was not determined by a pretreatment diagnosis or a re-assessment of the pulp status upon entry into the tooth; therefore both vital and necrotic cases, as well as those with and without periradicular pathosis, were included. Statistical analysis was carried out using Chi-square tests and considered variations in failure rates based on gender, provider, tooth type, position and arch. A t-test was used to evaluate data on age. The overall success rate was 89.2%. No statistically significant differences were seen based on gender, age, arch or provider. Statistically, anterior teeth were more successful than posterior teeth. [ABSTRACT FROM AUTHOR]

Since the mid-1980s, when juvenile arrests for violent crime increased dramatically, interest has focused on juvenile offenders who commit violent acts. Legislatures across the United States have enacted a variety of measures to "get tough" with juveniles in response to escalating crime rates and the perceptions that longer sentences were needed. This manuscript provides follow-up data on 59 juveniles who were committed to the adult Department of Corrections in Florida during the period January 1982 through January 1984 for one or more counts of murder, attempted murder, or, in a few cases, manslaughter. Although many of these adolescents received lengthy prison sentences, more than two-thirds had been released from prison prior to November 1999. This article presents data on amount of time served and recidivism over the 15 to 17 year period. Results indicated that 60 percent of sample subjects released from prison were returned to prison, and most of those who failed did so within the first three years of release. Findings from the present study, when examined in the context of previous comparative follow-up studies of delinquent youths, suggest that the dialogue on how to handle violent youths must be continued if juvenile homicide offenders are going to be released to society at some point in the future. [ABSTRACT FROM AUTHOR]

We examined the effect of protocatechuic acid (PCA) on methotrexate (MTX)‐induced testicular and epididymal toxicity in Wistar rats, treated with MTX (20 mg/kg) alone or in combination with PCA (25 and 50 mg/kg) body weight for a week. PCA significantly abated MTX‐mediated increase in reactive oxygen and nitrogen species generation and lipid peroxidation as well as enhances glutathione balance and antioxidant enzymes in the testes and epididymis of treated animals. PCA suppressed MTX‐mediated increases in interleukin‐1β, tumour necrosis factor alpha and caspase‐3 activity in treated animals. Additionally, PCA treatment mediated increases in luteinising and follicle‐stimulating hormones, prolactin and testosterone levels with marker enzymes of testicular function, accompanied with increase in sperm functionality in treated animals. Conclusively, PCA may serve as potential supplementation, enhancing reproductive health in males undergoing MTX therapy. [ABSTRACT FROM AUTHOR]

The present study investigated the impact of coexposure to fluoride and diethylnitrosamine (DEN) on hepatorenal function in adult rats. The animals were exposed to fluoride (15 mg/L in drinking water) and DEN (10 mg/kg) singly or coexposed to both compounds for 14 days. Results demonstrated that the fluoride or DEN mediated increase in hepatorenal toxicity was intensified in the coexposure group. Additionally, the decrease in antioxidant enzyme activities as well as the elevation in reactive oxygen and nitrogen species, and lipid peroxidation was markedly aggravated in rats coexposed to DEN and fluoride. Furthermore, the increase in levels of nitric oxide, tumor necrosis factor‐α and interleukin‐1β, myeloperoxidase and caspase‐3 activities as well as histological lesions was more pronounced in the liver and kidney of rats coexposed to DEN and fluoride. Conclusively, coexposure to fluoride and DEN exacerbated hepatorenal damage via enhancement of oxido‐inflammatory responses and caspase‐3 activation in rats. [ABSTRACT FROM AUTHOR]

Diethylnitrosamine (DEN) and cadmium are environmental contaminants of known poisonous consequences in animals and humans. We examined the influence of acute oral co‐exposure to DEN (10 mg/kg) and cadmium (5 mg/kg) on endocrine balance, semen and antioxidant status in rat testes. The results indicated decreases (p < 0.05) in the weight of the testis and organo‐somatic index of the testes in rats administered with either DEN or cadmium were aggravated in the co‐exposed rats. Serum concentrations of follicle‐stimulating hormone (FSH), luteinising hormone (LH) and testosterone decreased, and were more pronounced in rats co‐treated with DEN and cadmium. Enzymatic and non enzymatic antioxidant activities decreased following separate exposure to DEN and cadmium, and were increased in rats co‐treated with DEN and cadmium. The significant (p < 0.05) increases in malondialdehyde (MDA) was complemented by marked increase in sperm abnormalities, reduction in the sperm count, motility and viability compared with control. Histologically, co‐exposure to DEN and cadmium aggravates their discrete effects on the testes. Co‐exposure to DEN and cadmium elicited more severe endocrine disruption and testicular oxidative damage in rats, revealing additive adverse effects on testicular functions in rats and as such, may put exposed individual at greater risk. [ABSTRACT FROM AUTHOR]