Predicting mortality and recurrence in colorectal cancer: Comparative assessment of predictive models.

Introduction: Colorectal cancer (CRC), also known as colorectal cancer, is a significant disease marked by high fatality rates, ranking as the third leading cause of global mortality. The main objective of this study was to assess the accuracy of predictive models in predicting both mortality events and the probability of disease recurrence. Method: A retrospective analysis was conducted on a cohort of 284 individuals diagnosed with colorectal cancer between 2001 and 2017. Demographic and clinical data, including gender, disease stage, age at diagnosis, recurrence status, and treatment details, were meticulously recorded. We rigorously evaluated various predictive models, including Decision Trees, Random Forests, Random Survival Forests (RSF), Gradient Boosting, mboost, Deep Learning Neural Network (DLNN), and Cox regression. Performance metrics, such as sensitivity, positive predictive value (PPV), specificity, area under the receiver operating characteristic curve (ROC area), and overall accuracy, were calculated for each model to predict mortality and disease recurrence. The analysis was performed using R version 4.1.3 software and the Python programming language. Results: For mortality prediction, the mboost model demonstrated the highest sensitivity at 96.9% (95% CI: 0.83-0.99) and an ROC area of 0.88. It also exhibited high specificity at 80% (95% CI: 0.59-0.93), a positive predictive value of 86.1% (95% CI: 0.70-0.95), and an overall accuracy of 89% (95% CI: 0.78-0.96). Random Forests showed perfect sensitivity of 100% (95% CI: 0.85-1) but had low specificity at 0% (95% CI: 0-0.52) and poor overall accuracy (50%). On the other hand, DLNN had the lowest performance metrics for mortality prediction, with a sensitivity of 24% (95% CI: 0.222-0.268), specificity of 75% (95% CI: 0.73-0.77), and a lower positive predictive value of 42% (95% CI: 0.38-0.45). The Gradient Boosting model showed the best performance in predicting recurrence, achieving perfect sensitivity of 100% (95% CI: 0.87-1) and high specificity at 92.9% (95% CI: 0.76-0.99). It also had a high positive predictive value of 93.3% (95% CI: 0.77-0.99). Gradient Boosting, with an ROC area of 96.4%, and mboost, with an ROC area of 75%, demonstrated remarkable performance. DLNN had the lowest performance metrics for recurrence prediction, with sensitivity at 1.75% (95% CI: 0.01-0.02), specificity at 98% (95% CI: 0.97-0.98), and a lower positive predictive value at 52.6% (95% CI: 0.39-0.65). Conclusion: In summary, the mboost model demonstrated outstanding performance in predicting mortality, achieving exceptional results across various evaluation metrics. Random Forests exhibited perfect sensitivity but showed poor specificity and overall accuracy. The DLNN model displayed the lowest performance metrics for mortality prediction. In terms of recurrence prediction, the Gradient Boosting model outperformed other models with perfect sensitivity, high specificity, and positive predictive value. The DLNN model had the lowest performance metrics for recurrence prediction. Overall, the results emphasize the effectiveness of the mboost and Gradient Boosting models in predicting mortality and recurrence in colorectal cancer patients.

Exploring the impact of stage and tumor site on colorectal cancer survival: Bayesian survival modeling.

Colorectal cancer is a prevalent malignancy with global significance. This retrospective study aimed to investigate the influence of stage and tumor site on survival outcomes in 284 colorectal cancer patients diagnosed between 2001 and 2017. Patients were categorized into four groups based on tumor site (colon and rectum) and disease stage (early stage and advanced stage). Demographic characteristics, treatment modalities, and survival outcomes were recorded. Bayesian survival modeling was performed using semi-competing risks illness-death models with an accelerated failure time (AFT) approach, utilizing R 4.1 software. Results demonstrated significantly higher time ratios for disease recurrence (TR = 1.712, 95% CI 1.489-2.197), mortality without recurrence (TR = 1.933, 1.480-2.510), and mortality after recurrence (TR = 1.847, 1.147-2.178) in early-stage colon cancer compared to early-stage rectal cancer. Furthermore, patients with advanced-stage rectal cancer exhibited shorter survival times for disease recurrence than patients with early-stage colon cancer. The interaction effect between the disease site and cancer stage was not significant. These findings, derived from the optimal Bayesian log-normal model for terminal and non-terminal events, highlight the importance of early detection and effective management strategies for colon cancer. Early-stage colon cancer demonstrated improved survival rates for disease recurrence, mortality without recurrence, and mortality after recurrence compared to other stages. Early intervention and comprehensive care are crucial to enhance prognosis and minimize adverse events in colon cancer patients.

Survival prediction and prognostic factors in colorectal cancer after curative surgery: insights from cox regression and neural networks.

Medical research frequently relies on Cox regression to analyze the survival distribution of cancer patients. Nonetheless, in specific scenarios, neural networks hold the potential to serve as a robust alternative. In this study, we aim to scrutinize the effectiveness of Cox regression and neural network models in assessing the survival outcomes of patients who have undergone treatment for colorectal cancer. We conducted a retrospective study on 284 colorectal cancer patients who underwent surgery at Imam Khomeini clinic in Hamadan between 2001 and 2017. The data was used to train both Cox regression and neural network models, and their predictive accuracy was compared using diagnostic measures such as sensitivity, specificity, positive predictive value, accuracy, negative predictive value, and area under the receiver operating characteristic curve. The analyses were performed using STATA 17 and R4.0.4 software. The study revealed that the best neural network model had a sensitivity of 74.5% (95% CI 61.0-85.0), specificity of 83.3% (65.3-94.4), positive predictive value of 89.1% (76.4-96.4), negative predictive value of 64.1% (47.2-78.8), AUC of 0.79 (0.70-0.88), and accuracy of 0.776 for death prediction. For recurrence, the best neural network model had a sensitivity of 88.1% (74.4-96.0%), specificity of 83.7% (69.3-93.2%), positive predictive value of 84.1% (69.9-93.4%), negative predictive value of 87.8% (73.8-95.9%), AUC of 0.86 (0.78-0.93), and accuracy of 0.859. The Cox model had comparable results, with a sensitivity of 73.6% (64.8-81.2) and 85.5% (78.3-91.0), specificity of 89.6% (83.8-93.8) and 98.0% (94.4-99.6), positive predictive value of 84.0% (75.6-90.4) and 97.4% (92.6-99.5), negative predictive value of 82.0% (75.6-90.4) and 88.8% (0.83-93.1), AUC of 0.82 (0.77-0.86) and 0.92 (0.89-0.95), and accuracy of 0.88 and 0.92 for death and recurrence prediction, respectively. In conclusion, the study found that both Cox regression and neural network models are effective in predicting early recurrence and death in patients with colorectal cancer after curative surgery. The neural network model showed slightly better sensitivity and negative predictive value for death, while the Cox model had better specificity and positive predictive value for recurrence. Overall, both models demonstrated high accuracy and AUC, indicating their usefulness in predicting these outcomes.

Recurrence and Postoperative Death in Patients with Colorectal Cancer: A New Perspective via Semi-competing Risk Framework.

BACKGROUND/AIMS: Cancer studies suffer from an overestimation of prediction of survival when both recurrence and death are of interest. This longitudinal study aimed to mitigate this problem utilizing a semi-competing risk approach evaluating the factors affecting recurrence and postoperative death in patients with colorectal cancer. MATERIALS AND METHODS: This longitudinal prospective study was conducted in 284 patients with resected colorectal cancer who were referred to the Imam Khomeini Clinic in Hamadan, Iran, during 2001-2017. Primary outcomes were postoperative outcomes and patient survival, including time to recurrence (of colorectal cancer), time to death, and time to death after recurrence. All patients who were alive at the end of the study were censored for death and who did not experience recurrence of colorectal cancer were also censored for recurrent colorectal cancer. The relationship between underlying demographics and clinical factors and the outcomes was assessed using a semicompeting risk approach. RESULTS: The results of the multivariable analysis showed that having metastasis to other sites (hazard ratio = 36.03; 95% CI = 19.48- 66.64) and higher pathological node (pN) stage (hazard ratio = 2.46; 95% CI = 1.32-4.56) were associated with a raised hazard of recurrence. The fewer chemotherapies (hazard ratio = 0.39; 95% CI = 0.17-0.88) and higher pN stages (hazard ratio = 4.32; 95% CI = 1.27-14.75) showed significantly higher hazards of death without recurrence. Having metastasis to other sites (hazard ratio = 2.67; 95% CI = 1.24-5.74) and higher pN stages (hazard ratio = 1.91; 95% CI = 1.02-3.61) were linked with the higher hazard of death after recurrence. CONCLUSION: Considering findings on death /recu rrenc e-spe cific predictors obtained in this study to manage the outcomes in patients with colorectal cancer, tailored strategies for preventive and interventional plans should be deliberated.

Nail abnormalities in subepidermal blistering diseases: a cross-sectional study.

BACKGROUND: Nail involvement in subepidermal autoimmune blistering diseases (SEABD) is not common. Although these changes can be transient, permanent changes can also occur. This study addresses nail involvement manifestations and their associated factors in patients with SEABD. METHODS: From March 2020 to March 2021, we enrolled 56 patients with SEABD who were being examined at a tertiary skin hospital and checked their nail changes. We investigated the association between the SEABD subtypes and treatments that patients were receiving and the nail abnormalities. Additional factors including age, gender, duration since diagnosis, presence of mucosal involvement, and anti-bp230 and anti-bp180 IgG antibody quantitative levels (in those patients with bullous pemphigoid) were analyzed. RESULTS: The most common nail abnormalities were ridging, onycholysis, and onychoschizia. We observed a lower prevalence of onycholysis in EBA, a lower prevalence of periungual bullae in MMP, and a higher prevalence of scarring loss in EBA. Rituximab and dapsone were effective in preventing onycholysis as well as prednisolone in preventing subungual hematoma. Multiple lesions were found to be more common in the foot digits including great toes, probably because of higher exposure to trauma. CONCLUSIONS: In summary, in patients with SEABD and concomitant nail involvement, the underlying disease control, proper treatment, and avoidance of trauma may be helpful.

A bayesian approach to model the underlying predictors of early recurrence and postoperative death in patients with colorectal Cancer.

OBJECTIVE: This study aimed at utilizing a Bayesian approach semi-competing risks technique to model the underlying predictors of early recurrence and postoperative Death in patients with colorectal cancer (CRC). METHODS: In this prospective cohort study, 284 patients with colorectal cancer, who underwent surgery, referred to Imam Khomeini clinic in Hamadan from 2001 to 2017. The primary outcomes were the probability of recurrence, the probability of Mortality without recurrence, and the probability of Mortality after recurrence. The patients 'recurrence status was determined from patients' records. The Bayesian survival modeling was carried out by semi-competing risks illness-death models, with accelerated failure time (AFT) approach, in R 4.1 software. The best model was chosen according to the lowest deviance information criterion (DIC) and highest logarithm of the pseudo marginal likelihood (LPML). RESULTS: The log-normal model (DIC = 1633, LPML = -811), was the optimal model. The results showed that gender(Time Ratio = 0.764: 95% Confidence Interval = 0.456-0.855), age at diagnosis (0.764: 0.538-0.935 ), T3 stage (0601: 0.530-0.713), N2 stage (0.714: 0.577-0.935 ), tumor size (0.709: 0.610-0.929), grade of differentiation at poor (0.856: 0.733-0.988), and moderate (0.648: 0.503-0.955) levels, and the number of chemotherapies (1.583: 1.367-1.863) were significantly related to recurrence. Also, age at diagnosis (0.396: 0.313-0.532), metastasis to other sites (0.566: 0.490-0.835), T3 stage (0.363: 0.592 - 0.301), T4 stage (0.434: 0.347-0.545), grade of differentiation at moderate level (0.527: 0.387-0.674), tumor size (0.595: 0.500-0.679), and the number of chemotherapies (1.541: 1.332-2.243) were the significantly predicted the death. Also, age at diagnosis (0.659: 0.559-0.803), and the number of chemotherapies (2.029: 1.792-2.191) were significantly related to mortality after recurrence. CONCLUSION: According to specific results obtained from the optimal Bayesian log-normal model for terminal and non-terminal events, appropriate screening strategies and the earlier detection of CRC leads to substantial improvements in the survival of patients.

Clinical Characteristics and Treatment Outcomes of Scleromyxedema: A 10-Year Retrospective Survey.

Scleromyxedema is a rare but important mucinosis disorder of the skin that is presented with dermatological manifestations such as waxy papules, diffuse induration, and nondermatologic involvements like neurological and renal disorders. We report a case series of the data regarding the characteristics and treatment of 14 patients diagnosed with scleromyxedema and their follow-up. Patients entered the study based on scleromyxedema diagnosis criteria. Comorbidities were also recorded to evaluate their effect on the treatment process. Clinicopathological and laboratory findings and responses to their treatment were evaluated separately. There was a significant improvement after administering intravenous immunoglobulin (IVIG). Despite the lack of a definite treatment for this condition, the present study shows that the application of IVIG can improve both cutaneous and systemic symptoms. Younger patients, in particular, responded significantly to the use of IVIG. More studies are required to investigate the potential efficacy of IVIG in the treatment of scleromyxedema.

Effect of Selenium-Enriched Yeast Supplementation on Serum Thyroid-Stimulating Hormone and Anti-Thyroid Peroxidase Antibody Levels in Subclinical Hypothyroidism: Randomized Controlled Trial.

BACKGROUND: In the subclinical hypothyroidism, T4 or T3 levels are normal and thyroid-stimulating hormone (TSH) is slightly high. Selenium deficiency can lead to thyroid dysfunction. The present study aims to investigate the effect of selenium supplementation on the thyroid hormone and anti-thyroid peroxidase antibody (anti-TPO AB) levels. MATERIALS AND METHODS: In this double-blinded, randomized, placebo-controlled clinical trial, 42 patients with subclinical hypothyroidism were randomly assigned to receive 200 µg selenium or placebo for 8 weeks. In the both groups, the serum TSH and anti-TPO antibody levels were measured and assessed before and after the intervention. RESULTS: After the interventions, the mean serum TSH reduction in the intervention and placebo groups was -10.98 ± 33.31 and -3.20 ± 38.36, respectively, which were not statistically significant. However, the mean serum anti-TPO Ab concentration increased in the intervention and placebo groups (109.81 ± 51.49% vs. 173.17 ± 96.26%), between which the difference was not statistically significant (P >0.05) despite a slight increase in the mean anti-TPO level in the intervention group. CONCLUSION: The results of the current study indicated that selenium supplementation has no significant effect on serum anti-TPO Ab and TSH levels in the patients with subclinical hypothyroidism. Studies with larger sample size and with different doses of selenium are needed to reach more precise results.

Diagnosis of a 09 cm pheochromocytoma mistaken to be an intramesenteric pancreatic tumor: Case report complying with the scare guidelines.

INTRODUCTION: Pheochromocytoma is an adrenal medullary tumor of the chromaffin cells first described in 1886, remains an entity not fully discovered that case reports keep showing its diversity in clinical presentation, diagnosis methods treatment and follow up challenges. CASE PRESENTATION: We report the case of a 47 year old woman with complaining from abdominal pain and major weightless with a 09 cm tumor of the body of the pancreas viewed in imaging with no hormonal secretion but high levels of chromogranine A open surgery conducted that revealed the tumor to be located between the adrenal medulla and the Aorta misleading the team between an adrenal tumor or a zuckerkandl body tumor. The hemodynamic changes after manipulation of the tumor and the histopathology confirming the diagnosis of pheochromocytoma. Our main surprise was the aspect of the tumor bombing in the peritoneal cavity firstly thought to be mesenteric tumor; and the stability of the patient with no premedication until the tumor had been manipulated, enlarging the hypothesis about catecholamine secretion of these tumor. DISCUSSION: The diagnosis is basically simple when the tumor expresses its catecholamines by biomarkers testing, an imaging. Functional imaging should be used to locate the tumor or its metastasis, the sequence of testing or imaging can vary either it's a symptomatic tumor or an incidentaloma. Preoperative measures should be taken so no major preoperative complications and the main treatment is the tumor complete resection CONCLUSION: The malignancy of the pheochromocytoma is no near to be reliably identified which imposes a lifetime follow up of these patients as for metastasis were described even after 40 years after diagnosis.

Haptoglobin administration into the subarachnoid space prevents hemoglobin-induced cerebral vasospasm.

Delayed ischemic neurological deficit (DIND) is a major driver of adverse outcomes in patients with aneurysmal subarachnoid hemorrhage (aSAH), defining an unmet need for therapeutic development. Cell-free hemoglobin that is released from erythrocytes into the cerebrospinal fluid (CSF) is suggested to cause vasoconstriction and neuronal toxicity, and correlates with the occurrence of DIND. Cell-free hemoglobin in the CSF of patients with aSAH disrupted dilatory NO signaling ex vivo in cerebral arteries, which shifted vascular tone balance from dilation to constriction. We found that selective removal of hemoglobin from patient CSF with a haptoglobin-affinity column or its sequestration in a soluble hemoglobin-haptoglobin complex was sufficient to restore physiological vascular responses. In a sheep model, administration of haptoglobin into the CSF inhibited hemoglobin-induced cerebral vasospasm and preserved vascular NO signaling. We identified 2 pathways of hemoglobin delocalization from CSF into the brain parenchyma and into the NO-sensitive compartment of small cerebral arteries. Both pathways were critical for hemoglobin toxicity and were interrupted by the large hemoglobin-haptoglobin complex that inhibited spatial requirements for hemoglobin reactions with NO in tissues. Collectively, our data show that compartmentalization of hemoglobin by haptoglobin provides a novel framework for innovation aimed at reducing hemoglobin-driven neurological damage after subarachnoid bleeding.

Oral Candida colonization and plaque type psoriasis: Is there any relationship?

AIM: The potential role of superantigens derived from microbial agents could be considered in the pathogenesis of psoriasis, but the association between Candida albicans and psoriasis severity is still controversial. The present study was designed to compare the prevalence of oral candidiasis in a group of psoriatic patients and healthy patients, and its correlation with psoriasis severity. METHODS: Seventy psoriatic patients with no history of systemic treatment and 70 closely-matched control patients underwent oral examination. Scraping of oral mucosa to detect Candida species was done using a sterile cytobrush. RESULTS: Candida was detected in the oral cavity of 20% of patients with psoriasis and 2.8% of control cases (P = .002), but none had clinical features of oral candidiasis. Candida albicans was the only species isolated from the oral cavity of both groups. No correlation was found between sex, age, phototherapy, and presence of oral candidiasis. There was a positive correlation between psoriasis severity and colony count (P < .001). CONCLUSIONS: The prevalence of oral candidiasis is higher in psoriatic patients and is associated with disease severity. It is not exactly clear whether oral candidiasis can aggravate psoriasis or if psoriasis can predispose patients to oral candidiasis.

Determination of the formal redox potentials of the cyanhaemoglobin/cyanmethaemoglobin and the myoglobin/metmyoglobin couples at neutral pH.

Determination of a representative formal redox potential of the Fe(II)/Fe(III) redox couple in cyanhaemoglobin, at pH=7 and related to the state in solution, was the objective of this work. It was achieved at low concentrations of the protein (5µM) to circumvent undesired adsorption. Square-wave voltammetry instead of classical cyclic voltammetry was applied because this method is more sensitive and provides information on the formal redox potential and reversibility, even for rapid processes. We obtained E°'=-0.12±0.01V for cyanhaemoglobin and E°'=-0.10±0.01V, vs. SHE, for myoglobin in comparison. These values differ by only 20mV because the two Fe(II)/Fe(III) redox centres are embedded in closely resembling chemical environments. The small difference is probably owed to the additional axially coordinating cyanide ligand in cyanmethaemoglobin which slightly favours the Fe(III) state in the haem macrocycle.

Low-Temperature Trapping of Intermediates in the Reaction of NO• with O2.

The autoxidation of NO• was studied in glass-like matrices of 2-methylbutane at 110 K and in a 8:3 v/v mixture of 2,2-dimethylbutane and n-pentane (rigisolve) at 80-90 K, by letting gaseous NO• diffuse into these solvents that were saturated with O2. In 2-methyllbutane, we observed a red compound. However, in rigisolve at 85-90 K, a bright yellow color appears that turns red when the sample is warmed by 10-20 K. The new yellow compound is a precursor of the red one and also diamagnetic. The UV-vis spectrum of the yellow compound contains a band which resembles that present in ONOO-. Because the red and yellow intermediates are not paramagnetic, we postulate that O═N-O-O• is in close contact with NO•, or with another O═N-O-O•. Diffusion of gaseous O2 into rigisolve saturated with NO• does not produce a color; however, a weak EPR signal (g = 2.010) is observed. This signal most likely indicates the presence of ONOO•. These findings complement our earlier observation of a red color at low temperatures and the presence of ONOO• in the gas phase (Galliker, B.; Kissner, R.; Nauser, T.; Koppenol, W. H. Chem. Eur. J. 2009, 15, 6161-6168), and they indicate that the termolecular autoxidation of nitrogen monoxide proceeds via the intermediate ONOO• and not via N2O2.

Electrode Potentials of l-Tryptophan, l-Tyrosine, 3-Nitro-l-tyrosine, 2,3-Difluoro-l-tyrosine, and 2,3,5-Trifluoro-l-tyrosine.

Electrode potentials for aromatic amino acid radical/amino acid couples were deduced from cyclic voltammograms and pulse radiolysis experiments. The amino acids investigated were l-tryptophan, l-tyrosine, N-acetyl-l-tyrosine methyl ester, N-acetyl-3-nitro-l-tyrosine ethyl ester, N-acetyl-2,3-difluoro-l-tyrosine methyl ester, and N-acetyl-2,3,5-trifluoro-l-tyrosine methyl ester. Conditional potentials were determined at pH 7.4 for all compounds listed; furthermore, Pourbaix diagrams for l-tryptophan, l-tyrosine, and N-acetyl-3-nitro-l-tyrosine ethyl ester were obtained. Electron transfer accompanied by proton transfer is reversible, as confirmed by detailed analysis of the current waves, and because the slopes of the Pourbaix diagrams obey Nernst's law. E°'(Trp(•),H(+)/TrpH) and E°'(TyrO(•),H(+)/TyrOH) at pH 7 are 0.99 ± 0.01 and 0.97 ± 0.01 V, respectively. Pulse radiolysis studies of two dipeptides that contain both amino acids indicate a difference in E°' of approximately 0.06 V. Thus, in small peptides, we recommend values of 1.00 and 0.96 V for E°'(Trp(•),H(+)/TrpH) and E°'(TyrO(•),H(+)/TyrOH), respectively. The electrode potential of N-acetyl-3-nitro-l-tyrosine ethyl ester is higher, while because of mesomeric stabilization of the radical, those of N-acetyl-2,3-difluoro-l-tyrosine methyl ester and N-acetyl-2,3,5-trifluoro-l-tyrosine methyl ester are lower than that of tyrosine. Given that the electrode potentials at pH 7 of E°'(Trp(•),H(+)/TrpH) and E°'(TyrO(•),H(+)/TyrOH) are nearly equal, they would be, in principle, interchangeable. Proton-coupled electron transfer pathways in proteins that use TrpH and TyrOH are thus nearly thermoneutral.

Haptoglobin Preserves Vascular Nitric Oxide Signaling during Hemolysis.

RATIONALE: Hemolysis occurs not only in conditions such as sickle cell disease and malaria but also during transfusion of stored blood, extracorporeal circulation, and sepsis. Cell-free Hb depletes nitric oxide (NO) in the vasculature, causing vasoconstriction and eventually cardiovascular complications. We hypothesize that Hb-binding proteins may preserve vascular NO signaling during hemolysis. OBJECTIVES: Characterization of an archetypical function by which Hb scavenger proteins could preserve NO signaling during hemolysis. METHODS: We investigated NO reaction kinetics, effects on arterial NO signaling, and tissue distribution of cell-free Hb and its scavenger protein complexes. MEASUREMENTS AND MAIN RESULTS: Extravascular translocation of cell-free Hb into interstitial spaces, including the vascular smooth muscle cell layer of rat and pig coronary arteries, promotes vascular NO resistance. This critical disease process is blocked by haptoglobin. Haptoglobin does not change NO dioxygenation rates of Hb; rather, the large size of the Hb:haptoglobin complex prevents Hb extravasation, which uncouples NO/Hb interaction and vasoconstriction. Size-selective compartmentalization of Hb functions as a substitute for red blood cells after hemolysis and preserves NO signaling in the vasculature. We found that evolutionarily and structurally unrelated Hb-binding proteins, such as PIT54 found in avian species, functionally converged with haptoglobin to protect NO signaling by sequestering cell-free Hb in large protein complexes. CONCLUSIONS: Sequential compartmentalization of Hb by erythrocytes and scavenger protein complexes is an archetypical mechanism, which may have supported coevolution of hemolysis and normal vascular function. Therapeutic supplementation of Hb scavengers may restore vascular NO signaling and attenuate disease complications in patients with hemolysis.

Electrode reactions of iron oxide-hydroxide colloids.

Small-sized FeO(OH) colloids stabilised by sugars, commercially available for the clinical treatment of iron deficiency, show two waves during cathodic polarographic sweeps, or two current maxima with stationary electrodes, in neutral to slightly alkaline aqueous medium. Similar signals are observed with Fe(III) in alkaline media, pH > 12, containing citrate in excess. Voltammetric and polarographic responses reveal a strong influence of fast adsorption processes on gold and mercury. Visible spontaneous accumulation was also observed on platinum. The voltammetric signal at more positive potential is caused by Fe(III)→Fe(II) reduction, while the one at more negative potential has previously been assigned to Fe(II)→Fe(0) reduction. However, the involvement of adsorption phenomena leads us to the conclusion that the second cathodic current is caused again by Fe(III)→Fe(II), of species deeper inside the particles than those causing the first wave. This is further supported by X-ray photoelectron spectra obtained after FeO(OH) particle adsorption and reduction on a gold electrode surface. The same analysis suggests that sucrose stabilising the colloid is still bound to the adsorbed material, despite dilution and rinsing.

Water increases rates of epoxidation by Mn(III)porphyrins/imidazole/IO4(-) in CH2Cl2. Analogy with peroxidase and chlorite dismutase.

Manganese(III)-meso-tetraphenylporphyrin [Mn(TPP)] and manganese(III)-meso-tetrakis(pentafluorophenyl)porphyrin [Mn(TPFPP)] catalyse the epoxidation of cyclooctene by IO(4)(-) in the presence of excess imidazoles, in both dry CH(2)Cl(2) and CH(2)Cl(2) saturated with H(2)O. The reaction rates of the electron deficient Mn(TPFPP) are a factor 24 less than those of Mn(TPP); however, the former increases 15-30 times in the presence of water, while those of Mn(TPP) do so by a factor of 2-3. The most striking catalytic enhancement caused by the addition of water was observed with 2-methylimidazole and Mn(TPFPP). As deprotonation of imidazoles may play a significant role in the presence of water, we found that manganese(III)-meso-tetrakis(phenyl-4-sulfonato)porphyrin [Mn(TPPS)] decreases the NH proton pK(a) of axially coordinated imidazole from 14.2 to 9.5. We conclude that the imidazole ligand is partially deprotonated in the presence of water. The latter enables the solvation of imidazolium ions that are formed simultaneously. The imidazolate form of the co-catalyst is a much stronger donor than the imidazole itself, providing electron density to Mn(III) and thus promoting oxygen transfer. The failure of N-methylimidazole to increase the reaction rates upon addition of water supports this hypothesis. A functionally related deprotonation has been shown to occur in horseradish peroxidase (J. S. de Ropp, V. Thanabal, G. N. La Mar, J. Am. Chem. Soc. 1985, 107, 8270-8272) and in chlorite dismutase (B. R. Goblirsch, B. R. Streit, J. L. Dubois, C. M. Wilmot, J. Biol. Inorg. Chem. 2010, 15, 879-888). Mn(III)porphyrins in combination with imidazoles and water constitute a functional biomimetic model of peroxidases.