Evaluation of the biomechanics of Aramany class I obturators of different designs using numerical and experimental methods. Part I: Retention and associated stress.

STATEMENT OF PROBLEM: Studies on the biomechanics of obturators in the currently used designs of Aramany class I defect are lacking. Also, modifications of the designs presently used in unilateral palatal defects are needed to produce a prosthesis with more retention and less stress on the abutments. PURPOSE: The purpose of part I of this study was to differentiate among Aramany class I obturators of 4 designs regarding retention and associated stress using numerical and experimental methods. MATERIAL AND METHODS: Four finite element models and 36 different base obturators were fabricated and divided into 9 acrylic resin bases retained with Adams clasps and 9 linear, 9 tripodal, and 9 fully tripodal design obturators from casts obtained from a scanned skull. After modification, the prostheses were fabricated on the casts obtained from a 3-dimensionally printed cast. The retention was evaluated, and the data were collected and analyzed using a statistical software program (α=.05). The displacement and associated stress in the assorted casts were compared by using 5-N displacing force at 3 points using finite element analysis. The quantitative assessment was made by measuring the displacement and von Mises stress distribution on the prostheses and their supporting structures. The qualitative analysis was done by using a visual color mapping to depict stress location and intensity. RESULTS: No significant differences were found between fully tripodal (4.478 ±2.303 MPa) and tripodal obturators (4.478 ±2.286 MPa; P=.153), although fully tripodal showed more resistance to anterior displacement (4.522 ±0.979 and 3.553 ±1.58 MPa for fully tripodal and tripodal designs, respectively; P=.007), and tripodal obturators produced more resistance to middle displacement (5.441 ±1.778 and 2.784 ±0.432 MPa for tripodal and fully tripodal design respectively; P=.001). The fully tripodal obturator showed more retention (3.736 ±1.182 MPa) than the linear one (2.493 ±1.052 MPa; P=.001). The maxillary central incisor was the most stressed abutment, followed by the lateral incisor, while the second molar was the least. CONCLUSIONS: Regarding retention, the fully tripodal obturator produces retention comparable with the tripodal and significantly more than the linear. Acrylic resin prostheses retained with Adams clasps may be similar to metal-based prostheses regarding retention and stress distribution on the supporting structures.

Assessment of macular microvascular changes in children following treatment of anisometropic myopic amblyopia using optical coherence tomography angiography.

PURPOSE: To evaluate macular microvascular changes in the form of foveal avascular zone (FAZ) area and vessel density in the superficial, deep capillary plexuses, and choriocapillaris using optical coherence tomography angiography (OCTA) in children with anisometropic myopic amblyopia before and after treatment. METHODS: This prospective observational study included 32 patients younger than 12 years old with anisomyopic amblyopia. OCTA was done before patients' treatment with optical correction with or without patching and was repeated after successful amblyopia treatment. Outcomes included superficial, deep, and choriocapillaris vessel density (VD) and superficial and deep FAZ areas. RESULTS: The study included 13 males (40.6%) and 19 females (59.4%), and the mean age was 9.52 ± 1.33 years. Fifty-three percent (53%) of patients needed only optical correction, and the remaining 47% needed additional patching therapy. After successful treatment, there was a significant improvement in amblyopic eyes in best-corrected visual acuity (p < 0.001), with higher VD values in superficial capillary plexuses (p < 0.001), deep capillary plexuses (p < 0.001), and foveal choriocapillaris (p = 0.030). In the glasses with patching subgroup, the difference between pre-treatment and post-treatment parameters revealed a significant improvement in vessel density in superficial retinal plexuses (foveal and parafoveal; p values 0.023 and < 0.001, respectively) and deep retinal plexuses (whole image, foveal, and parafoveal; p values 0.003, < 0.001, and 0.002, respectively). While amblyopic eyes treated with glasses alone had a significantly greater difference in choriocapillaris foveal VD (p value = 0.022). CONCLUSION: After effective amblyopia treatment, amblyopic eyes exhibited improved best-corrected visual acuity and better macular perfusion along the superficial, deep vascular density, and choriocapillaris foveal VD. CLINICAL TRIAL REGISTRATION: CinicalTrials.gov Identifier: NCT05223153.

Amenorrhea, premenstrual tension syndrome, and dysmenorrhea among women of reproductive age on hemodialysis: A national study in Egypt.

BACKGROUND AND AIM: The current literature concerning the reproductive health of end stage renal disease (ESRD) females is scarce, outdated, and largely unknown in women living in developing countries. This study aims to estimate the prevalence of menstrual abnormalities and their associated factors among ESRD women in reproductive age undergoing chronic hemodialysis (HD) in Egypt. METHODS: Thirty-five dialysis centers were selected by simple random sampling to represent the different regions of Egypt. Non-pregnant women in the reproductive age (15-50 years) receiving dialysis at the participating centers completed a questionnaire about their menstrual health during a routine hemodialysis session. Their responses were verified by reviewing the medical records and assessing their clinical data. RESULTS: Out of the 472 women, 32.6% had amenorrhea. Menstrual irregularities were reported in 37% of the menstruating women. Premenstrual tension syndrome (PMS) was reported in 70% while dysmenorrhea in 58%. Amenorrhea was more prevalent in non-working women who started hemodialysis after the age of 30. PMS was more encountered in women with hypertension or in those with obstructive uropathy or autoimmune disease as a cause of ESRD. Dysmenorrhea was more prevalent among patients with autoimmune disease or chronic hepatitis C virus and those who started dialysis after the age of 30. CONCLUSION: Secondary amenorrhea, dysmenorrhea, and PMS are common among premenopausal women with ESRD on dialysis. Several factors including socio-economic factors, cause of ESRD, and hypertension contribute to these disorders. Future studies are needed to understand the underlying pathophysiologic mechanisms and management of these abnormalities.

Does Radial Artery Cannulation Affect the Perfusion of the Dominant Hand in Adult Patients with Normal Modified Allen's Test Undergoing Cardiac Surgeries? Data Derived from the Peripheral Perfusion Index.

OBJECTIVES: This study aimed to evaluate the effect of radial artery cannulation on hand perfusion in patients with normal modified Allen's test undergoing cardiac surgeries using cardiopulmonary bypass (CPB). DESIGN: Prospective follow-up study. SETTING: Single institution, Assiut University Cardiothoracic Hospital. PARTICIPANTS: Forty-nine patients who underwent cardiac surgeries using cardiopulmonary bypass were enrolled. INTERVENTIONS: Cannulation of radial artery in the dominant hand using a 20-gauge catheter. MEASUREMENTS AND MAIN RESULTS: The primary outcomes were the mean peripheral perfusion index (PPI) >60 seconds (mean PPI60) and the thumb temperature, which were measured at different times before and during the surgery. There was a statistically significant difference in the mean PPI60 between both hands (p = 0.033). Before skin incision, the mean PPI60 was significantly higher in the noncannulated hand (p < 0.001). Also, there was a statistically significant difference in the thumb temperature between both hands (p = 0.013). At low core body temperature, the thumb temperature was significantly lower in the noncannulated hand (p = 0.017). CONCLUSIONS: In adult patients undergoing cardiac surgeries using CPB, even with normal modified Allen's test, radial artery cannulation may affect the perfusion of the dominant hand, especially at low arterial blood pressure or low core body temperature. Since the PPI is one of the noninvasive methods used for intraoperative assessment of the peripheral perfusion, the authors recommend the use of the noncannulated hand for this purpose to not misguide this assessment.

Thin-Flap Laser In Situ Keratomileusis-Associated Dry Eye: A Comparative Study Between Femtosecond Laser and Mechanical Microkeratome-Assisted Laser In Situ Keratomileusis.

OBJECTIVE: To assess and compare postlaser in situ keratomileusis (LASIK) dry eye after LASIK with planned thin flaps created by a femtosecond laser (FS) and mechanical microkeratome (MK). METHODS: Patients were stratified according to the flap creation technique into FS and MK groups with planned 100 µm flap thickness in all eyes. Dry eye parameters including tear film break-up time (TBUT), Schirmer I test, ocular surface disease index (OSDI), and lower tear meniscus height and area (tear meniscus height [TMH] and tear meniscus area [TMA]) were assessed before surgery and at 3 and 6 months after surgery. RESULTS: The study included 102 eyes of 55 patients (52 eyes underwent FS-LASIK/50 eyes underwent MK-LASIK). The preoperative characteristics including age, gender, and spherical equivalents were similar in both groups (P>0.05). The difference in postoperative flap thickness was statistically significant (P<0.05). In each group, dry eye parameters showed a statistically significant worsening (P value<0.001) at 3 months with later significant improvement at 6 months but did not return to baseline. The mean TBUT, Schirmer I, and lower TMH and TMA were statistically higher, and the mean OSDI was statistically lower in FS-LASIK than the MK-LASIK group at both 3 and 6 months (P value<0.001). The depth of ablation had a statistically significant correlation with Schirmer I at 6 months and OSDI at both 3 and 6 months post-LASIK (P<0.05). CONCLUSION: The use of femtosecond laser technology in performing thin-Flap LASIK eye surgeries has improved the outcome of post-LASIK dry eye when compared with the mechanical microkeratome.

High-sensitivity troponin in the evaluation of patients with suspected acute coronary syndrome: a stepped-wedge, cluster-randomised controlled trial.

BACKGROUND: High-sensitivity cardiac troponin assays permit use of lower thresholds for the diagnosis of myocardial infarction, but whether this improves clinical outcomes is unknown. We aimed to determine whether the introduction of a high-sensitivity cardiac troponin I (hs-cTnI) assay with a sex-specific 99th centile diagnostic threshold would reduce subsequent myocardial infarction or cardiovascular death in patients with suspected acute coronary syndrome. METHODS: In this stepped-wedge, cluster-randomised controlled trial across ten secondary or tertiary care hospitals in Scotland, we evaluated the implementation of an hs-cTnI assay in consecutive patients who had been admitted to the hospitals' emergency departments with suspected acute coronary syndrome. Patients were eligible for inclusion if they presented with suspected acute coronary syndrome and had paired cardiac troponin measurements from the standard care and trial assays. During a validation phase of 6-12 months, results from the hs-cTnI assay were concealed from the attending clinician, and a contemporary cardiac troponin I (cTnI) assay was used to guide care. Hospitals were randomly allocated to early (n=5 hospitals) or late (n=5 hospitals) implementation, in which the high-sensitivity assay and sex-specific 99th centile diagnostic threshold was introduced immediately after the 6-month validation phase or was deferred for a further 6 months. Patients reclassified by the high-sensitivity assay were defined as those with an increased hs-cTnI concentration in whom cTnI concentrations were below the diagnostic threshold on the contemporary assay. The primary outcome was subsequent myocardial infarction or death from cardiovascular causes at 1 year after initial presentation. Outcomes were compared in patients reclassified by the high-sensitivity assay before and after its implementation by use of an adjusted generalised linear mixed model. This trial is registered with ClinicalTrials.gov, number NCT01852123. FINDINGS: Between June 10, 2013, and March 3, 2016, we enrolled 48 282 consecutive patients (61 [SD 17] years, 47% women) of whom 10 360 (21%) patients had cTnI concentrations greater than those of the 99th centile of the normal range of values, who were identified by the contemporary assay or the high-sensitivity assay. The high-sensitivity assay reclassified 1771 (17%) of 10 360 patients with myocardial injury or infarction who were not identified by the contemporary assay. In those reclassified, subsequent myocardial infarction or cardiovascular death within 1 year occurred in 105 (15%) of 720 patients in the validation phase and 131 (12%) of 1051 patients in the implementation phase (adjusted odds ratio for implementation vs validation phase 1·10, 95% CI 0·75 to 1·61; p=0·620). INTERPRETATION: Use of a high-sensitivity assay prompted reclassification of 1771 (17%) of 10 360 patients with myocardial injury or infarction, but was not associated with a lower subsequent incidence of myocardial infarction or cardiovascular death at 1 year. Our findings question whether the diagnostic threshold for myocardial infarction should be based on the 99th centile derived from a normal reference population. FUNDING: The British Heart Foundation.

Macular vessels density in diabetic retinopathy: quantitative assessment using optical coherence tomography angiography.

PURPOSE: The aim of this study was to evaluate macular perfusion using OCTA automated software algorithms; vessel area density (VD) and non-flow tool to measure FAZ area in treatment-naïve diabetic eyes with moderate or severe NPDR and having macular edema, and correlate these parameters with LogMAR (logarithm of the minimum angle of resolution) visual acuity. Diabetic eyes without macular edema were included, to detect and define differences within the parameters between diabetic eyes with and without macular edema. METHODS: Forty-five diabetic eyes with diabetic macular edema, forty diabetic eyes without macular edema, and forty eyes of healthy controls were examined using OCTA (RTVue-XR Avanti; Optovue, Inc, Fremont, CA). The macular vessel area density (VD) and foveal avascular zone (FAZ) area were assessed and statistically compared between the three groups and also correlated with the foveal thickness and visual acuity. Data were entered and analyzed by SPSS 19. Quantitative data were presented as mean and standard deviation, and qualitative data presented as frequency distribution; independent samples t test, Chi square test and Pearson correlation were done. RESULTS: Mean whole image VD was 44.4 ± 3.6 in diabetic eyes with DME, 45.6 ± 4.2 in diabetics without DME, and 49 ± 3.9 in control eyes (P = 0.001). Diabetic eyes with DME had significantly lower vessels density values at the level of the deep retinal plexus (in the parafoveal, superior hemi, inferior hemi, temporal, superior, and nasal areas), when compared with diabetic eyes without DME. In diabetic eyes with DME, significant fair negative correlation was found between whole image vessels density at the level of the superficial retinal plexus and LogMAR VA (r = - 0.313, P = 0.036). Also, a significant fair positive correlation was found between FAZ area (at both the superficial and deep retinal plexus) and LogMAR visual acuity, in diabetic eyes with DME, where eyes with larger FAZ area had worse vision (P = 0.005 and P = 0.016, respectively). Diabetic eyes with DME had significantly larger FAZ area at the level of the superficial capillary plexus (mean superficial FAZ ± SD 0.55 ± 0.25) than diabetic eyes without edema (mean superficial FAZ ± SD 0.41 ± 0.12) and control subjects (mean superficial FAZ ± SD 0.35 ± 0.09). CONCLUSION: Using OCTA machine with AngioAnalytics parameters (vessel area density and non-flow area) helped in objective quantification of macular perfusion and accurately measuring the FAZ area in diabetic eyes with macular edema. Both parameters were significantly correlated with visual function in treatment-naïve diabetic eyes with edema. These OCTA biomarkers could be used to predict visual function in such eyes, to monitor response to treatment.

Oxidative Stress Attenuates Lipid Synthesis and Increases Mitochondrial Fatty Acid Oxidation in Hepatoma Cells Infected with Hepatitis C Virus.

Cytopathic effects are currently believed to contribute to hepatitis C virus (HCV)-induced liver injury and are readily observed in Huh7.5 cells infected with the JFH-1 HCV strain, manifesting as apoptosis highly correlated with growth arrest. Reactive oxygen species, which are induced by HCV infection, have recently emerged as activators of AMP-activated protein kinase. The net effect is ATP conservation via on/off switching of metabolic pathways that produce/consume ATP. Depending on the scenario, this can have either pro-survival or pro-apoptotic effects. We demonstrate reactive oxygen species-mediated activation of AMP-activated kinase in Huh7.5 cells during HCV (JFH-1)-induced growth arrest. Metabolic labeling experiments provided direct evidence that lipid synthesis is attenuated, and ß-oxidation is enhanced in these cells. A striking increase in nuclear peroxisome proliferator-activated receptor α, which plays a dominant role in the expression of ß-oxidation genes after ligand-induced activation, was also observed, and we provide evidence that peroxisome proliferator-activated receptor α is constitutively activated in these cells. The combination of attenuated lipid synthesis and enhanced ß-oxidation is not conducive to lipid accumulation, yet cellular lipids still accumulated during this stage of infection. Notably, the serum in the culture media was the only available source for polyunsaturated fatty acids, which were elevated (2-fold) in the infected cells, implicating altered lipid import/export pathways in these cells. This study also provided the first in vivo evidence for enhanced ß-oxidation during HCV infection because HCV-infected SCID/Alb-uPA mice accumulated higher plasma ketones while fasting than did control mice. Overall, this study highlights the reprogramming of hepatocellular lipid metabolism and bioenergetics during HCV infection, which are predicted to impact both the HCV life cycle and pathogenesis.

A Refined Model of the HCV NS5A protein bound to daclatasvir explains drug-resistant mutations and activity against divergent genotypes.

Many direct-acting antiviral agents (DAAs) that selectively block hepatitis C virus (HCV) replication are currently under development. Among these agents is Daclatasvir, a first-in-class inhibitor targeting the NS5A viral protein. Although Daclatasvir is the most potent HCV antiviral molecule yet developed, its binding location and mode of binding remain unknown. The drug exhibits a low barrier to resistance mutations, particularly in genotype 1 viruses, but its efficacy against other genotypes is unclear. Using state-of-the-art modeling techniques combined with the massive computational power of Blue Gene/Q, we identified the atomic interactions of Daclatasvir within NS5A for different HCV genotypes and for several reported resistant mutations. The proposed model is the first to reveal the detailed binding mode of Daclatasvir. It also provides a tool to facilitate design of second generation drugs, which may confer less resistance and/or broader activity against HCV.

Acute and long-term effects of arsenite in HepG2 cells: modulation of insulin signaling.

Epidemiological studies have indicated a relationship between the prevalence of diabetes and exposure to arsenic. Mechanisms by which arsenic may cause this diabetogenic effect are largely unknown. The phosphoinositide 3'-kinase (PI3K)/Akt signaling pathway plays an important role in insulin signaling by controlling glucose metabolism, in part through regulating the activity of FoxO transcription factors. The present study aimed at investigating the effect of short and long-term exposure to arsenite on insulin signaling in HepG2 human hepatoma cells, the role of PI3K/Akt signaling therein and the modulation of target genes controlled by insulin. Exposure of cells to arsenite for 24 h rendered cells less responsive toward stimulation of Akt by insulin. At the same time, short-term exposure to arsenite induced a concentration-dependent increase in phosphorylation of Akt at Ser-473, followed by phosphorylation of FoxO proteins at sites known to be phosphorylated by Akt. Phosphorylation of FoxOs was prevented by wortmannin, pointing to the involvement of PI3K. Arsenite exposure resulted in attenuation of FoxO DNA binding and in nuclear exclusion of FoxO1a-EGFP. A 24-h exposure of HepG2 cells to submicromolar concentrations of arsenite resulted in downregulation of glucose 6-phosphatase (G6Pase) and selenoprotein P (SelP) mRNA levels. Curiously, arsenite had a dual effect on SelP protein levels, inducing a small increase in the nanomolar and a distinct decrease in the micromolar concentration range. Interestingly, arsenite-induced long-term effects on G6Pase and SelP mRNA or SelP protein levels were not blocked by the PI3K inhibitor, wortmannin. In conclusion, arsenite perturbs cellular signaling pathways involved in fuel metabolism: it impairs cellular responsiveness toward insulin, while at the same time stimulating insulin-like signaling to attenuate the expression of genes involved in glucose metabolism and the release of the hepatokine SelP, which is known to modulate peripheral insulin sensitivity.

Acute arsenic treatment alters arachidonic acid and its associated metabolite levels in the brain of C57Bl/6 mice.

The toxic effects of arsenic on the whole brain, as well as the discrete regions, has been previously reported for mice. We investigated the effects of acute arsenite (As(III)) on brain levels of arachidonic acid (AA) and its associated metabolites generated through cytochrome P450 (CYP), cyclooxygenase (COX), and lipoxygenase (LOX) pathways. Our results demonstrated that acute As(III) treatment (12.5 mg·(kg body mass)(-1)) decreases cytosolic phospholipase A2 (cPLA2) with a subsequent decrease in its catalytic activity and brain AA levels. In addition, As(III) differentially altered CYP epoxygenases and CYP ω-hydroxylases, but it did not affect brain Ephx2 mRNA or sEH catalytic activity levels. As(III)-mediated effects on Cyps caused an increase in brain 5,6-epoxyeicosatrienoic acid (5,6-EET) and 16/17-hydroxyeicosatetreinoic acid (16/17-HETE) levels, and a decrease in 18- and 20-HETE levels. Furthermore, As(III) increased cyclooxygenase-2 (COX-2) mRNA while decreasing prostaglandins F2α (PGF2α) and PGJ2. As(III) also increased brain 5-lipoxygenase (5-LOX) and 15-LOX mRNA, but decreased 12-LOX mRNA. These changes in LOX mRNA were associated with a decrease in 8/12-HETE levels only. In conclusion, this is the first demonstration that As(III) decreases AA levels coinciding with alterations to EET, HETE, and PG levels, which affects brain development and neurochemistry.

New graduate nurses' readiness for practice, transition and integration into the workplace: A longitudinal study with mixed methods research.

AIM: To examine the readiness of new graduate nurses for practice and evaluate factors influencing their transition into the workplace. BACKGROUND: This is new research in Bahrain. Understanding readiness for practice is important during a time when there is a national initiative to promote nursing as a career among the indigenous Bahraini population. The worldwide nursing shortages and aging workforce require new and innovative recruitment and retention measures. There is change, increased demand and complexity, in nursing and healthcare needs with accompanying healthcare specialization. In such a health care environment, the transitioning and readiness of newly qualified nurses is an increasing challenge. DESIGN: A longitudinal design, with a triangulated, mixed methods, research approach was used. METHODS: The study population consisted of 50 newly graduated nurses. Data were collected over one year through self-administered questionnaires, reflective diaries and focus groups. Quantitative data were analysed using SPSS and qualitative data using thematic analysis with adherence to GRAMMS reporting guidelines. RESULTS: In Bahrain, there are actions to recruit young Arabic students to nursing including schools and community presentations by trained nurse ambassadors, social media activities and career exhibitions, however there is a lack of objective information on the perspective of cohorts of nurses who have successfully completed graduate nursing registration programmes and transitioned into practice. International literature suggests that the transition of newly graduated nurses can be stressful and challenging. On entry to practice, the respondents positively perceived their characteristics and attributes; however, their confidence was affected by challenges in the workplace. The transitioning of the new graduate nurses was affected by the availability of support and leadership, induction programmes and the new complex work environment. CONCLUSION: Understanding work readiness and the emotional needs of new graduate nurses, accompanied by improved support, will enhance the transition of newly qualified nurses into the workplace and reduce attrition. STUDY REGISTRATION: KHUH/Research/No.279/2019.

Botulinum toxin augmented surgery versus conventional surgery in the management of large-angle concomitant esotropia: A randomized clinical trial.

BACKGROUND: The surgical management of large-angle concomitant esotropia is challenging with high reoperation rates. This study aims to assess the effectiveness and safety of intraoperative botulinum toxin A (BTA) augmentation compared to surgery alone in large angle concomitant esotropia. MATERIALS AND METHODS: This is a prospective randomized interventional study. Patients with large angle concomitant esotropia (≥55 prism diopter [PD]) were randomly allocated to either surgery only (Group I) or BTA augmented surgery (Group II). The surgical effect in PD/mm was calculated and compared between the study groups at all follow up intervals. Treatment was considered successful if the patients had orthotropia ± 10 PD at their final examinations. RESULTS: A total of 23 patients were included in the study, 11 in Group I and 12 in group II. The surgical effect was significantly greater in Group II compared to Group I at all follow up durations. The 1-year surgical effect was 32.5% greater in Group II compared to Group I (5.99 ± 0.69 vs. 4.52 ± 0.91 PD/mm, respectively, P = 0.001). The success rate was greater for Group II compared to Group I (75% vs. 63.64%, respectively), but this difference was not statistically significant (P = 0.901). CONCLUSION: Botulinum toxin augmented surgery is a good alternative to surgery alone in the treatment of large angle concomitant esotropia. BTA injection exerts a significant augmentation effect on medial rectus muscle recessions.

Performance evaluation of two different software programs for automated ASPECTS scoring in patients with suspected stroke.

BACKGROUND: The range of software available to radiologists has increased enormously with the advancement of AI. A good example of this is software to determine ASPECTS in the treatment of potential stroke patients. OBJECTIVE: In this study, two software packages (eASPECTS from Brainomix and VIA_ASPECTS from Siemens) were tested and compared for their performance in the daily clinical routine of a maximum care provider with a 24/7 stroke unit. METHODS: A total of 637 noncontrast CT images were obtained from consecutive patients with suspected stroke, of whom 73 were finally diagnosed with MCA infarction. Differences in agreement and quantification of agreement were analysed, as well as the correlation and sensitivity, specificity and accuracy compared to raters. RESULTS: Compared to VIA_ASPECTS, eASPECTS shows good agreement and strong correlation with the raters. VIA_ASPECTS has lower accuracy and low specificity than eASPECTS but a higher sensitivity. CONCLUSION: Both software products have the potential to be decision support tools for radiologists. There are, however, differences between the two software products in terms of their intended use.

Mercury modulates the cytochrome P450 1a1, 1a2 and 1b1 in C57BL/6J mice: in vivo and in vitro studies.

In the current study C57BL/6J mice were injected intraperitoneally with Hg(2+) in the absence and presence of TCDD. After 6 and 24h the liver was harvested and the expression of Cyps was determined. In vitro, isolated hepatocytes were incubated with TCDD in the presence and absence of Hg(2+). At the in vivo level, Hg(2+) significantly decreased the TCDD-mediated induction of Cyps at 6h while potentiating their levels at 24h. In vitro, Hg(2+) significantly inhibited the TCDD-mediated induction of Cyp1a1 in a concentration- and time-dependent manner. Interestingly, Hg(2+) increased the serum hemoglobin (Hb) levels in mice treated for 24h. Upon treatment of isolated hepatocytes with Hb alone, there was an increase in the AhR-dependent luciferase activity with a subsequent increase in Cyp1a1 protein and catalytic activity levels. Importantly, when hepatocytes were treated for 2h with Hg(2+) in the presence of TCDD, then the medium was replaced with new medium containing Hb, there was potentiation of the TCDD-mediated effect. In addition, Hg(2+) increased heme oxygenase-1 (HO-1) mRNA, which coincided with a decrease in the Cyp1a1 activity level. When the competitive HO-1 inhibitor, tin mesoporphyrin was applied to the hepatocytes there was a partial restoration of Hg(2+)-mediated inhibition of Cyp1a1 activity. In conclusion, we demonstrate for the first time that there is a differential modulation of the TCDD-mediated induction of Cyp1a1 by Hg(2+) in C57BL/6J mice livers and isolated hepatocytes. Moreover, this study implicates Hb as an in vivo specific modulator of Cyp1 family.

Modulation of cytochrome P450 1 (Cyp1) by vanadium in hepatic tissue and isolated hepatocyte of C57BL/6 mice.

The objective of the current study was to investigate the effect of vanadium (V(5+)) on Cyp1 expression and activity in C57BL/6 mice liver and isolated hepatocytes. For this purpose, C57BL6 mice were injected intraperitoneally with V(5+) (5 mg/kg) in the absence and presence of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (15 µg/kg) for 6 and 24 h. Furthermore, isolated hepatocytes from C57BL6 mice were treated with V(5+) (5, 10, and 20 µM) in the absence and presence of TCDD (1 nM) for 3, 6, 12, and 24 h. In vivo, V(5+) alone did not significantly alter Cyp1a1, Cyp1a2, or Cyp1b1 mRNA, protein, or catalytic activity levels. Upon co-exposure to V(5+) and TCDD, V(5+) significantly potentiated the TCDD-mediated induction of the Cyp1a1, Cyp1a2, and Cyp1b1 mRNA, protein, and catalytic activity levels at 24 h. In vitro, V(5+) decreased the TCDD-mediated induction of Cyp1a1 mRNA, protein, and catalytic activity levels. Furthermore, V(5+) significantly inhibited the TCDD-induced AhR-dependent luciferase activity. V(5+) also increased serum hemoglobin (Hb) levels in animals treated for 24 h. Upon treatment of isolated hepatocytes with Hb alone or in the presence of TCDD, there was an increase in the AhR-dependent luciferase activity. When isolated hepatocytes were treated for 2 h with V(5+) in the presence of TCDD, followed by replacement of the medium with new medium containing Hb, there was further potentiation to the TCDD-mediated effect. The present study demonstrates that there is a differential modulation of Cyp1a1 by V(5+) in C57BL/6 mice livers and isolated hepatocytes and demonstrates Hb as an in vivo specific modulator.

Acute arsenic treatment alters cytochrome P450 expression and arachidonic acid metabolism in lung, liver and kidney of C57Bl/6 mice.

1. Arsenic (As(III)) toxicity has received increasing attention as human exposure to arsenic is associated with pulmonary, hepatic and renal toxicities. Therefore, in the present study, we investigated the effect of acute As(III) treatment on pulmonary, hepatic and renal cytochrome (CYP) P450-mediated arachidonic acid metabolism. 2. Our results demonstrated that acute As(III) treatment (12.5 mg/kg) altered CYP epoxygenases, CYP ω-hydroxylases and EPHX2 mRNA levels that were isozyme and tissue specific. 3. Furthermore, As(III) increased the formation of epoxyeicosatrienoic acids (EETs) in the kidney without affecting their levels in the lung or liver. In addition, acute As(III) treatment increased dihydroxyeicosatrienoic acid (DHETs) formation in the lung, while it did not affect liver DHETs formation and decreased kidney DHETs formation. 4. As(III) also increased total epoxygenases activity in the lung while it decreased its levels in the kidney and had no effect on the liver. Furthermore, As(III) increased 20-hydroxyeicosatetraenoic acid formation in the liver while it decreased its formation in the kidney. 5. Lastly, As(III) increased soluble epoxide hydrolase activity in the lung, while it decreased its levels in the kidney and had no effect on the liver. In conclusion, this is the first demonstration that As(III) alters arachidonic acid metabolism in a tissue specific manner.

Modulation of aryl hydrocarbon receptor-regulated genes by acute administration of ammonium metavanadate in kidney, lung and heart of C57BL/6 mice.

We recently reported that vanadium (V(5+) ) was able to decrease the 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-mediated induction of Cyp1a1 and Nqo1 at mRNA, protein and catalytic activity levels in mouse hepatoma Hepa 1c1c7 and human hepatoma HepG2 cells. However, little is known regarding the in vivo effects. Thus, the objective of this study was to investigate whether similar effects would occur at the in vivo level. Therefore, we examined the effect of exposure to V(5+) (5 mg kg(-1) ) with or without TCDD (15 µg kg(-1) ) on the AhR-regulated genes in kidney, lung and heart of C57BL/6 J mice. Our results demonstrated that V(5+) alone significantly decreased Cyp1b1 protein and catalytic activity levels in kidney at 24 h. Moreover, it significantly potentiated Nqo1 and Gsta1 gene expression in the heart, and only Gsta1 gene expression in the lung. Upon co-exposure, we found that V(5+) significantly inhibited the TCDD-mediated induction of Cyp1a1, Cyp1a2 and Cyp1b1 mRNA, protein and catalytic activity levels in the kidney at 24 h. On the other hand, V(5+) significantly potentiated the TCDD-mediated induction of Nqo1 and Gsta1 protein and activity levels in the kidney. Cyp1a1, Cyp1b1, Nqo1 mRNA, protein and catalytic activity levels in the lung were significantly potentiated at 6 h. Interestingly, all tested genes in the heart were significantly decreased at 6 h with the exception of Gsta1 mRNA. The present study demonstrates that V(5+) modulates TCDD-induced AhR-regulated genes. Furthermore, the effect on one of these enzymes could not be generalized to other enzymes even if it was in the same organ.

A case report of pedal monkeypox in a HIV patient: A challenging diagnosis with a misleading history.

Pedal Monkeypox is a disease which can mimic many other pedal conditions. It should always be considered in differential diagnosis. A young male HIV patient who presented with a tender foot lesion and diagnosed with pedal Monkeypox as a result of performed tests is discussed hereby in the case report. We expect that this case report adds to the existing literature on this subject.