Assessment of toxicity using dehydrogenases activity and mathematical modeling

Dehydrogenase activity is frequently used to assess the general condition of microorganisms in soil and activated sludge. Many studies have investigated the inhibition of dehydrogenase activity by various compounds, including heavy metal ions. However, the time after which the measurements are carried out is often chosen arbitrarily. Thus, it can be difficult to estimate how the toxic effects of compounds vary during the reaction and when the maximum of the effect would be reached. Hence, the aim of this study was to create simple and useful mathematical model describing changes in dehydrogenase activity during exposure to substances that inactivate enzymes. Our model is based on the Lagergrens pseudo-first-order equation, the rate of chemical reactions, enzyme activity, and inactivation and was created to describe short-term changes in dehydrogenase activity. The main assumption of our model is that toxic substances cause irreversible inactivation of enzyme units. The model is able to predict the maximum direct toxic effect (MDTE) and the time to reach this maximum (T_MDTE). In order to validate our model, we present two examples: inactivation of dehydrogenase in microorganisms in soil and activated sludge. The model was applied successfully for cadmium and copper ions. Our results indicate that the predicted MDTE and T_MDTE are more appropriate than EC₅₀ and IC₅₀ for toxicity assessments, except for long exposure times.     

Just-in-Time Evidence-Based E-mail “Reminders” in Home Health Care: Impact on Patient Outcomes

OBJECTIVE: To assess the impact and cost-effectiveness of two information-based provider reminder interventions designed to improve self-care management and outcomes of heart failure (HF) patients. DATA SOURCES/STUDY SETTING: Interview and agency administrative data on 628 home care patients with a primary diagnosis of HF. STUDY DESIGN: Patients were treated by nurses randomly assigned to usual care or one of two intervention groups. The basic intervention was an e-mail to the patient's nurse highlighting six HF-specific clinical recommendations. The augmented intervention supplemented the initial nurse reminder with additional clinician and patient resources. DATA COLLECTION: Patient interviews were conducted 45 days post admission to measure self-management behaviors, HF-specific outcomes (Kansas City Cardiomyopathy Questionnaire-KCCQ), health-related quality of life (EuroQoL), and service use. PRINCIPAL FINDINGS: Both interventions improved the mean KCCQ summary score (15.3 and 12.9 percent, respectively) relative to usual care (p< or =.05). The basic intervention also yielded a higher EuroQoL score relative to usual care (p< or =.05). In addition, the interventions had a positive impact on medication knowledge, diet, and weight monitoring. The basic intervention was more cost-effective than the augmented intervention in improving clinical outcomes. CONCLUSIONS: This study demonstrates the positive impact of targeting evidence-based computer reminders to home health nurses to improve patient self-care behaviors, knowledge, and clinical outcomes. It also advances the field's limited understanding of the cost-effectiveness of selected strategies for translating research into practice.     

Minilaparoscopy-assisted natural orifice surgery.

BACKGROUND AND OBJECTIVES: New technology has allowed us to perform major abdominal and pelvic surgeries with increasingly smaller instruments. The ultimate goal is surgery with no visible scars. Until current technical limitations are overcome, minilaparoscopy-assisted natural orifice surgery (MANOS) provides a solution. The aim of this study was to examine our clinical and experimental experience with MANOS. METHOD: Minilaparoscopic abdominal instruments were used together with a large vaginal port, which was used for insufflation, visual purposes, introduction of operative instruments, and specimen extraction. Minilaparoscopy-assisted intraperitoneal transgastric appendectomy was done in simulators (Lap trainer with SimuVision, Simulab Corp., Seattle, WA). RESULTS: Since 1998, we have used this technique in 100 cases including ovarian cystectomies, oophorectomies, salpingo-oophorectomies, myomectomies, appendectomies, and cholecystectomies. Some oophorectomies were performed after vaginal hysterectomy in cases where vaginal extraction was not possible. In this case series, we had only one complication, a case of postoperative fever after an ovarian cystectomy, which was diagnosed as drug-related fever. Our limited simulator experience showed that MANOS is a feasible technique for performing transgastric appendectomies. CONCLUSION: It may take several years for natural orifice surgery to become standard care. Meanwhile, MANOS could encourage and expedite this process.     

Exchangeable magnesium pool masses in healthy women: effects of magnesium supplementation.

BACKGROUND: Studying magnesium pools in the body with use of stable isotopes may be helpful for evaluating magnesium status. Data on the evaluation of magnesium pools in humans are scarce. OBJECTIVE: We undertook this study to evaluate the effects of a magnesium supplementation program on the size of the exchangeable body pools of magnesium and on classic indexes of magnesium status in healthy women with normal magnesium status. DESIGN: Ten healthy women participated in a kinetic study with magnesium stable isotopes before and after 8 wk of magnesium supplementation. Each woman received 3 supplements containing 5.08 mmol (122 mg) elemental Mg/d (366 mg/d). Before and at the end of the supplementation period, each woman received an intravenous injection of 1.67 mmol (40 mg) (25)Mg, and the plasma magnesium disappearance curve was followed for the next 7 d. Two methods were used to analyze the exchangeable pools of magnesium: 1) formal multicompartmental modeling and 2) a simplified estimation of the total mass of the rapidly exchangeable magnesium pool (EMgP). RESULTS: In these healthy women, exchangeable magnesium pools represented 11-12% of total body magnesium on the basis of multicompartmental analysis. The simplified estimation of EMgP overestimated the size of the exchangeable magnesium pools by approximately 45-50%. Eight weeks of magnesium supplementation did not significantly modify the size of the exchangeable magnesium pools, whereas urinary magnesium excretion was significantly higher after 8 wk of supplementation. CONCLUSION: Women with no clinical evidence of magnesium deficiency may not respond to short-term supplementation with increases in the mass of the exchangeable magnesium body pool or in magnesium turnover rates.     

Nephrology and renal replacement therapy in Romania--transition still continues (Cinderella story revisited).

INTRODUCTION. This report describes the current status of nephrology and renal replacement therapy (RRT) in Romania, a country with previously limited facilities, highlighting national changes in the European context. METHODS: Trends in RRT development were analysed in 2003, on a national basis, using the same questionnaires as in previous surveys (1991, 1995). Survival data and prognostic risk factors were calculated retrospectively from a large representative sample of 2284 patients starting RRT between January 1, 1995 and December 31, 2001 (44% of the total RRT population investigated). RESULTS: In 2003, RRT incidence [128 per million population (p.m.p.)] and prevalence (250 p.m.p.) were six and five times higher, respectively, than in 1995. The annual rate of increase in the stock of RRT patients (11%) was supported mainly by an exponential development of the continuous ambulatory peritoneal dialysis (CAPD) population (+600%), while the haemodialysis (HD) growth rate was stable (+33%) and renal transplantation made a marginal contribution. Renal care infrastructure followed the same trend: nephrology departments (+100%) and nephrologists (+205%). The characteristics of RRT incident patients changed accordingly to current European epidemiology (increasing age and prevalence of diabetes and nephroangiosclerosis). The estimated overall survival of RRT patients in Romania was 90.6% at 1 year [confidence interval (CI) 89.4-91.8] and 62.2% at 5 years (CI 59.4-65.0). Patients' survival was negatively influenced (Cox regression analysis) by age >65 years (P < 0.001), lack of pre-dialysis monitoring by a nephrologist [P = 0.01, hazards ratio (HR) = 0.8], severe anaemia, lack of erythropoetin treatment (P < 0.001, HR = 0.6), and co-morbidity, e.g. cardiovascular diseases (P < 0.001, HR = 1.8) and diabetes mellitus (P < 0.001, HR = 2.2). CONCLUSIONS: Although the rate of increase in RRT patient stock in 1996-2003 in Romania was the highest in Europe, the prevalence remained below the European mean. As CAPD had the greatest expansion, followed by HD, an effective transplantation programme must be set up to overcome the imbalance. The quality of RRT appears to be good and survival was similar to that in other registries. Further evolution implies strategies of prevention, based on national surveys, supported by the Romanian Renal Registry.     

Catabolism of newly synthesized decorin in vitro by human peritoneal mesothelial cells.

OBJECTIVE: Previous studies have shown that decorin and biglycan account for over 70% of the proteoglycans (PGs) synthesized by human peritoneal mesothelial cells (HPMCs). Since these PGs are involved in the control of cell growth, cell differentiation, and matrix assembly, we investigated their turnover in cultured HPMCs. METHODS: Confluent HPMCs were metabolically labeled with [35S]-sulfate and the labeled products isolated from the cell medium and the cell layer characterized by sensitivity to bacterial eliminases. Experiments were undertaken with exogenous labeled decorin, and its metabolic state was studied. RESULTS: In a 24-hour labeling period, 75% of the newly synthesized chondroitin sulfate/dermatan sulfate (CS/DS) PGs appeared in the culture medium, the majority of which (90%) was decorin. In the cell layer, protein-free glycosaminoglycan (GAG) chains accounted for 21% of the total CS/DS at 24 hours and exhibited constant specific activity at 12-16 hours. The latter material was turned over with a half-life of approximately 2.5 hours. Exogenous decorin underwent receptor-mediated endocytosis and subsequent intracellular degradation. Uptake but not degradation could be inhibited by heparin. CONCLUSIONS: HPMCs are distinguished by a rapid turnover of decorin. A characteristic metabolic feature is the existence of a large intracellular pool of protein-free DS-GAGs. Understanding the control of decorin turnover in HPMCs might lead to delineation of its potential role in both the physiology and pathophysiology of the membrane in PD patients.     

Psychosocial factors associated with poor diabetes self-care management in a specialized Center in Mexico City

To examine the relationship between demographic, clinical and psychosocial variables and diabetes self-care management in Mexican type 2 diabetic patients. Cross-sectional study of 176 consecutive patients with type 2 diabetes aged 30-75 years, attending a tertiary health-care center in Mexico City. A brief medical history and previously validated questionnaires were completed. The study group consisted of 64 males/112 females, aged 55 +/- 11 years, mean diabetes duration of 12 +/- 8 years and HbA1c of 9.0 +/- 2.0%, 78.4% reported following the correct dose of diabetes pills or insulin, 58% ate the recommended food portions, and 44.3% did exercise three or more times per week. A good adherence to these three recommendations was observed in only 26.1% of the patients. These patients considered as a group were characterized by a greater knowledge about the disease (P < 0.00001), regular home blood glucose monitoring (P < 0.01), an inner perception of better diabetes control (P = 0.007), good health (P = 0.004) and better communication with their physician (P < 0.02). A poor adherence to two or the three main diabetes care recommendations was associated with a depressive state (OR 2.38, 95% CI 1.1-4.9, P < 0.01) and a history of excessive alcohol intake (OR 4.03, 95% CI 1.1-21.0, P = 0.03). Poor adherence to standard diabetes care recommendations is frequently observed in patients with type 2 diabetes attending a specialized health care center in Mexico City. Depression must be identified and treated effectively.     

Comparative studies on the amino acid derivatives of indometacin

A series of amino acid derivatives of indometacin (IND) was investigated in regard to their protein binding and prostaglandin synthetase inhibition in vitro, and to acute toxicity, anti-inflammatory, antiedemic, analgesic actions, and the influence on the central nervous system in vivo. In biochemical tests the compounds were several times less potent than IND. They differed among themselves in the respect of toxicity, which was always much lower than that of IND. Out of eight compounds investigated N-IND-glycine (K1) and N-IND-epsilon-aminocaproic acid (K5) exerted more favorable antiedemic and analgesic action than IND did. Both the derivatives only weakly inhibited the cotton-pellet granuloma formation. K1 acted similarly to IND in the arthritis test. K1, K5 and IND similarly irritated the gastric mucosa. A modification of IND structure by introduction of glycine or epsilon-aminocaproic acid resulted in two new anti-inflammatory agents of more favorable therapeutic index in the antiedemic and analgesic action and of much lower toxicity than the reference compound.