Reliability of telemedicine evaluation for EDSS functional systems in multiple sclerosis.

Introduction: There was an increase in telemedicine during the COVID-19 pandemic to follow patients with multiple sclerosis (MS). However, there is scarce data if online evaluations can cover important information assessed during in-clinic appointments, especially the Expanded Disability Status Score (EDSS). This study aims to develop a remote evaluation tool for EDSS functional systems and compare the performance with face-to-face evaluations. Methods: This was a single-center study that included all MS patients followed up at outpatient clinics of Hospital São Lucas Pontifícia Universidade Católica do Rio Grande do Sul, between April and August 2022. Initially, patients were routinely in-clinic evaluated by one trained neurologist for EDSS. After, patients were evaluated remotely without any information about the in-clinic EDSS results. We used a standardized interview with an interactive video platform to evaluate EDSS functional systems by telemedicine. Results: Forty-nine participants completed the two steps. Intra-class coefficient was 0.97 (95% CI: 0.95-0.98), concordance for EDSS below 4.0 was 0.87 (95% CI: 0.77-0.93) and ≥4.0 was 0.97 (95% CI: 0.89-0.99). There was perfect agreement in the final EDSS in 71.4% of the online and in-clinic evaluations. In the multivariate analysis, the visual (beta = 0.453; p = 0.003) and pyramidal (beta = 0.403; p = 0.009) systems contributed significantly to the difference in the final EDSS. Conclusion: The telemedicine tool created in this study can detect changes in functional systems with reliable results compared to in-clinic EDSS assessment. Telemedicine evaluations may reduce the number of in-clinic visits and the disease burden for patients with MS.

Local perceptions do not follow rainfall trends: A case study in traditional Marajo island communities (eastern para state, BR).

The great current challenge for the conservation and use of natural resources refers to global climate change, because of its impacts felt in different intensities at global, regional, and local spatial scales. Within the system of environmental protection areas in Brazil, the extractive reserves ensure the sustainable use of natural resources by traditional populations, thus maintaining the cultural and biological aspects of a region. Such populations, being in close management of the surrounding environments, tend to perceive changes in ecological processes that many need for their livelihoods. The use of this perception of local populations in conjunction with academic research evidence has a high potential to allow a whole and systemic view of possible changes in natural phenomena. This study developed an integrated analysis of scientific evidence and local perceptions to understand the variation of precipitation in a community inserted in an extractive reserve in the eastern Amazon. We used 30 years of precipitation data from the Brazilian National Institute of Meteorology - INMET, the Southern Oscillation Index - SOI, and the Atlantic Meridional Mode Index - AMM. Furthermore, we applied a form to measure the population's perception of possible changes in rainfall cycles in the region. The meteorological data indicate that the region of the community has been presenting a rainfall reduction; however, people in the community do not perceive this trend. Although it is public knowledge that the global climate is undergoing changes, a fact noted after the integrating analysis of scientific evidence with local knowledge in Resexmar Soure is that the perceptions of traditional populations often focus on smaller temporal and spatial scale visions.

Anti-protozoal activity of diamine derivatives.

Ten N-monoalkylated diamines were synthesized and evaluated for in vitro activities against Trichomonas vaginalis and Giardia lamblia. Several compounds displayed a good inhibition of parasite growth, with MIC less or equal to 20µg/mL. N-hexadecil-1,4-butanediamine was found to be the most active compound in vitro against T. vaginalis with MIC of 2.5µg/mL, twice more active in comparison to the reference drug metronidazole (MTZ). Seven of the studied compounds showed a better anti-G. lamblia activity than MTZ.

Potentiation of antifungal activity of amphotericin B by essential oil from Cinnamomum cassia.

The antifungal activity of the essential oil from Cinnamomum cassia, alone or combined with amphotericin B, a drug widely used for most indications despite side-effects was investigated. The composition of the oil was analysed by GC/MS and characterized by its very high content of cinnamaldehyde (92.2%). The minimal inhibitory concentration (MIC 80%), used to evaluate the antifungal activity against Candida albicans, was determined by a macrobroth dilution method followed by a modelling of fungal growth. The essential oil of Cinnamomum cassia exhibited strong antifungal effect (MIC 80% = 0.169 microL/mL and K(aff) = 18,544 microL/mL). A decrease of the MIC 80% of amphotericin B was obtained when the culture medium contained essential oil concentrations ranging from 0.08 to 0.1 microL/mL. The strongest decrease (70%) was obtained when the medium contained 0.1 microL/mL of essential oil. This potentiation of amphotericin B obtained in vitro may show promise for the development of less toxic and more effective therapies especially for the treatment of HIV infection.

Antifungal effect of various essential oils against Candida albicans. Potentiation of antifungal action of amphotericin B by essential oil from Thymus vulgaris.

The antifungal effect of the essential oil from Satureja montana L., Lavandula angustifolia Mill., Lavandula hybrida Reverchon, Syzygium aromaticum (L.) Merril and Perry, Origanum vulgare L., Rosmarinus officinalis L. and six chemotypes of Thymus vulgaris L. on Candida albicans growth were studied. The most efficiency was obtained with the essential oil from Thymus vulgaris thymol chemotype (MIC 80% = 0.016 microL/mL and Kaff = 296 microL/mL). The presence in the culture medium of essential oil from Thymus vulgaris thymol chemotype (0.01, 0.1, 0.2, 0.3 microg/mL) and amphotericin B involved a decrease of the MIC 80% of amphotericin B. In contrast, the combination of amphotericin B and low concentrations (0.00031-0.0025 microg/mL) of essential oil was antagonistic. The strongest decrease (48%) of the MIC 80% was obtained with medium containing 0.2 microL/mL of essential oil. These results signify that the essential oil of Thymus vulgaris thymol chemotype potentiates the antifungal action of amphotericin B suggesting a possible utilization of this essential oil in addition to antifungal drugs for the treatment of mycoses.

Antifungal effect of Hevea brasiliensis latex with various fungi. Its synergistic action with amphotericin B against Candida albicans.

Antifungal activity of latex from Hevea brasiliensis was observed with various fungi in macrobroth dilution assays. The strongest antifungal effect was obtained with Trichosporon cutaneum (MIC 80% = 40.615 microg protein ml(-1), Kaff = 0.075 microg(-1) protein ml) and Cryptococcus neoformans (MIC 80% = 56.078 microg protein ml(-1), Kaff = 0.059 microg(-1) protein ml). Amphotericin B was synergized with all H. brasiliensis latex concentrations tested. The rates of synergy were about 50, 44 and 55% with 15, 30 and 60 microg protein ml(-1) latex, respectively. The putative role of glycosidase activities measured in crude latex, especially alpha-d-mannosidase and N-acetyl-beta-d-glucosaminidase activities which are potentially able to split off intraparietal linkages between glycosidic residues, is discussed. The possible role of another antifungal factor associated with rubber particles of latex is suggested.

Mathematical modelling of antifungal action.

In this paper a simplified modelling approach indicated that yeast growth was inhibited by an antifungal drug according to an exponential function. In addition, the corresponding inhibition rate followed a hyperbolic function the parameters of which permit us to determine the percentage of maximum inhibition and the minimum inhibitory concentration for 80%. From the equation of a hyperbola it was also possible to calculate an affinity constant Kaff corresponding to the inverse of the concentration of antifungal drugs giving half the maximal inhibition. The affinity constant was demonstrated to be characteristic of the yeast strain and of the antifungal drug employed. Simulation of the mathematical modelling enabled determination of a theoretical inhibition level corresponding to strong concentrations of antifungal drugs which cannot be carried out for technical reasons (precipitates, opacity etc.). The interest of this mathematical modelling of growth and inhibition to predict the doses of antifungals which can act synergistically is discussed.

Enhanced antifungal activity of ketoconazole by Euphorbia characias latex against Candida albicans.

The in vitro suseptibility of Candida albicans to ketoconazole and Euphorbia characias latex alone or in combination was tested using the macrobroth dilution method. The MIC 80% of crude latex and ketoconazole are respectively 159 microg protein/ml and 0.3901 microg/ml. This method permits us to determine an affinity constant K(aff) for crude latex (0.015 microg(-1) protein ml) and ketoconazole (23.828 microg(-1) ml). The utilization of a mixture of latex at several concentrations (7.8-15.62-31.25-62.5 and 125 microg protein/ml) and ketoconazole indicates a synergistic effect between latex and ketoconazole. For latex concentrations of 31.25 and 62.5 microg protein/ml the MIC 80% of ketoconazole were inferior (0.194 and 0.183 microg/ml respectively) to that obtained with ketoconazole alone (0.390 microg/ml). A synergistic effect is therefore obtained between ketoconazole on the one hand and two concentrations of Euphorbia characias latex.

Blood reduced glutathione (GSH) concentrations in healthy and ill subjects.

BACKGROUND: Recently blood reduced glutathione (GSH), an important cellular antioxidant, has been proposed as an indicator of health, particularly in the elderly. To date, a gold standard unit for the expression of GSH concentrations is not known. The aim of the study is to define the most sensitive laboratory expression of GSH. EXPERIMENTAL DESIGN: a comparative study among some laboratory expressions of GSH. SETTING: Geriatric and Internal Medicine Units; General Community. PATIENTS AND PARTICIPANTS: forty-eight inpatients from Geriatric and Internal Medicine Units and 82 healthy subjects recruited among medical students and residents, people from preventive medicine services and from local senior centres. EXCLUSION CRITERIA FOR HEALTHY SUBJECTS: use of drugs in the year prior to the study. INTERVENTIONS: neither treatment nor interventions. MEASURES: the laboratory expression of GSH, compared in this study, were mg/dl, packed cell volume (PCV), mg/1010 RBC, mM/gHb. RESULTS: We noted statistically significant differences only if GSH was calculated as mg/1010 RBC; higher values were found in healthy subjects than in inpatients, apart from age. This modality of expression is minimally affected by haematological parameters; the low sensibility of the other modalities may be due to variations of MCV and Hb. Instead, the ratio GSH mg/1010 RBC expresses the true GSH concentrations inside each erythrocyte. This modality of expression is minimally affected by haematological parameters; the low sensibility of the other modalities may be due to variations of MCV and Hb.

Cystatin C, beta 2-microglobulin, and retinol-binding protein as indicators of glomerular filtration rate: comparison with plasma creatinine.

BACKGROUND: The aim of this study was to assess the diagnostic accuracy of plasma levels of three low-molecular weight proteins cystatin C, beta 2-microglobulin, and retinol-binding protein, as indicators of impairment of glomerular filtration rate in comparison with plasma creatinine. METHODS: Glomerular filtration rate (GFR) was measured in 110 patients (51 M and 59 F, aged 18--79 years); creatinine (Creat), cystatin C (Cys), beta 2-microglobulin (beta 2M), and retinol-binding protein (RBP) were determined on the same day. The correlation coefficients between the different markers and GFR were determined. Receiver-operating characteristics (ROC) analysis was performed to assess their diagnostic accuracy. Furthermore, the relationship between plasma levels of the examined markers of GFR and body weight, height, fat-free mass (FFM) and body cell mass (BCM) was determined. FFM and BCM were calculated by means of total body electrical impedance measurement. RESULTS: Serum concentrations of Cys, beta 2M and RBP increase progressively with the reduction of GFR. The magnitude of the increase in blood levels of Creat and beta 2M was higher than the increase of Cys, and much more than that of RBP, in particular in patients with GFR<20 ml/min/1.73 m(2). The correlation coefficients between GFR and 1/plasma concentrations were 0.647 for Creat, 0.651 for Cys, 0.731 for beta 2M, and 0.406 for RBP. ROC analysis indicated that the accuracy of beta 2M and Cys, as indicators of different degrees of GFR impairment (<80, <60, and <40 ml/min per 1.73 m(2)), was similar to that of Creat, while the diagnostic accuracy of RBP resulted significantly lower than that of Creat for any level of GFR. In patients without renal failure (GFR>40 ml/min per 1.73 m(2)), plasma concentrations of Creat were positively correlated with body weight (P<0.01), height (P<0.01), FFM (P<0.001) and BCM (P<0.001). Serum concentrations of RBP resulted correlated with FFM (P<0.05) and BCM (P<0.05), while no correlation was found between anthropometric data and Cys and beta 2M. CONCLUSION: Cystatin C and beta 2-microglobulin have a diagnostic accuracy very similar to that of creatinine, while retinol-binding protein is not an adequate marker of glomerular filtration.

Antifungal action of Hevea brasiliensis latex. Its effect in combination with fluconazole on Candida albicans growth.

Latex from Hevea brasiliensis and its subcellular fractions (L-serum and C-serum) were tested for antifungal activity alone or in combination with fluconazole. Candida albicans growth was inhibited with the same efficacy when yeasts were inoculated into culture medium supplemented over the total growth phase with latex as when latex was added during the exponential phase only: the minimum inhibitory concentration (MIC 80%) of H. brasiliensis latex was 123 micrograms protein ml-1. By means of a non-linear regression analysis of the experimental data, two distinct fixation sites for fluconazole (FCZ) could be determined: one of strong affinity (Kaff = 0.0162 microgram-1 protein ml) and another of low affinity (Kaff = 0.0071 microgram-1 protein ml). After addition of a mixture of FCZ and latex during the exponential phase, the affinity constant of yeasts for FCZ was calculated: when latex was in a final concentration of 21 micrograms protein ml-1 (Kaff = 1 microgram-1 protein ml) or 42 micrograms protein ml-1 (Kaff = 0.277 microgram-1 protein ml) and without latex (Kaff = 0.0502 microgram-1 protein ml). In two cases a synergistic effect between latex and FCZ was obtained. The highest efficacy was obtained with a latex concentration of 21 micrograms protein ml-1. The addition of subcellular fractions of latex, L-serum and C-serum, did not cause an antifungal effect. The indispensable role of rubber particles for raising an antifungal effect is demonstrated. Electron microscopy observations indicated a limited cell wall degradation and a high percentage of coagulated yeasts.

Enzymatic and physiological properties of the tungsten-substituted molybdenum TMAO reductase from Escherichia coli.

The trimethylamine N-oxide (TMAO) reductase of Escherichia coli is a molybdoenzyme that catalyses the reduction of the TMAO to trimethylamine (TMA) with a redox potential of +130 mV. We have successfully substituted the molybdenum with tungsten and obtained an active tungsto-TMAO reductase. Kinetic studies revealed that the catalytic efficiency of the tungsto-substituted TMAO reductase (W-TorA) was increased significantly (twofold), although a decrease of about 50% in its kcat was found compared with the molybdo-TMAO reductase (Mo-TorA). W-TorA is more sensitive to high pH, is less sensitive to high NaCl concentration and is more heat resistant than Mo-TorA. Most importantly, the W-TorA becomes capable of reducing sulphoxides and supports the anaerobic growth of a bacterial host on these substrates. The evolutionary implication and mechanistic significance of the tungsten substitution are discussed.

[Comparative analysis of 2 thromboplastins]. / Analisi comparativa di due tromboplastine.

BACKGROUND: This study was performed to evaluate the prothrombin time in normal healthy people (102 subjects) by means of two thromboplastins. METHODS: Dade Thromboplastin IS (rabbit brain thromboplastin) and Dade Innovin (recombinant tissue factor) were used. Derived fibrinogen, Claus fibrinogen and in vitro sensibility of these thromboplastins to known amount of heparin were also measured. RESULTS: A different behaviour of prothrombin time measurement linked to different thromboplastin sensibility connected to the age was observed. A different fibrinogen (Claus and derived) behaviour connected to the age that may help to explain thromboplastin sensibility difference with the age was also observed. Finally different sensibility of these two thromboplastins to heparin in vitro was observed. CONCLUSIONS: This result should be considered when anticoagulation is started with oral anti coagulant drug and heparin together.

[A new test for monitoring heparin therapy]. / Un nuovo test per il monitoraggio della terapia eparinica.

A simple and easy assay for plasma heparin measurement (international units/ml) is described. The method is based upon the heparin neutralization and titration by polybrene. Heparin biological activity is measured first by activated partial thromboplastin time prolongment and then by means of polybrene titration: plasma heparin concentration was evaluated in international units/ml (IU/ml). The design and properties of this method are reported. Application in clinical practice of monitoring heparinization during hemodialysis is evaluated.

Urinary excretion of proteins and tubular enzymes in renal transplant patients.

The aim of this study was to evaluate, in renal transplant recipients with different function of the graft, the urinary excretion of some low molecular weight proteins and tubular enzymes frequently employed as indicators of tubular dysfunction. Urinary excretion of proteins and enzymes was measured in 51 renal transplant patients and, for comparison, in 73 patients affected by different kidney diseases with various degrees of renal function. Values of urinary beta 2-microglobulin and retinol-binding protein higher than normal were found in most transplanted patients, even in those with good renal function. On the other hand, in renal patients the urinary excretion of low molecular weight proteins was high only when creatinine clearance was lower than 30 mL/min/1.73 m2. Furthermore, an increased urinary excretion of tubular enzymes was found in a higher number of transplanted patients than of renal patients. This behavior was particularly evident for lysosomal enzyme N-acetyl-beta-D-glucosaminidase. In conclusion, a tubular dysfunction occurs in the transplanted kidneys, even in those with well preserved glomerular function.

Gamma-glutamyltransferase is a reliable marker for tubular effects of contrast media.

The aim of this study was to evaluate the usefulness of the measurement of urinary excretion of the brush-border enzyme gamma glutamyl-transferase (GGT), in comparison with that of alanine aminopeptidase (AAP), as a marker for tubular toxicity due to contrast media (CM). Urinary activities of AAP and GGT were measured prior to the administration of CM and 1, 3 and 5 days after in forty-nine adult renal patients undergoing a radiological examination with intravascular administration of CM. The behavior of GGT was similar to that of AAP. In fact, urinary activities of both AAP and GGT increased greatly after CM. This effect was maximal on the 1st day and statistically significant for both enzymes. Furthermore, on the 1st day a relevant increase of enzyme activity (at least +50% over the basal value) was observed in the same number of patients (67%) for AAP and GGT. The concordance between GGT and AAP variations was high and statistically significant. Finally, different variables (osmolarity, dose of CM, and baseline renal function of the patients) had a similar effect on urinary excretion of AAP and GGT. The repeatability of duplicated determinations of GGT resulted better than that of AAP. In conclusion, the good concordance of the results of GGT with those of AAP justifies the use of GGT as a marker for tubular effects due to CM. Furthermore, the measurement of GGT has a better repeatability than that of AAP.

Safety and efficacy anticoagulation in extracorporeal hemodialysis by simultaneous administration of low-dose prostacyclin and low molecular weight heparin.

BACKGROUND: The aim of this work is to describe an approach allowing extracorporeal hemodialysis (HD) with administration of low molecular weight heparin (LMWH) and to compare the dialyzer efficiency of this approach versus infractionated heparin (UFH) used alone. METHODS: Low molecular weight heparin (Nadroparin, molecular weight 4500 d) administered in a single injection (dose 3075 IU AXa) plus prostacyclin (Epoprostenol sodium salt, molecular weight 375 d) by continuous infusion (3 ng/kg/min) have been used as anticoagulants during hemodialysis in 8 patients. In comparison, standard continuous heparinization by unfractionated heparin was used. Hemodialysis efficiency (dialyzer clearance for urea, creatinine, uric acid and phosphate), coagulation (activated partial thromboplastin time, antithrombin III, fibrinogen platelet count, prothrombin time) and hemodynamic parameters (blood arterial pressure and heart rate) were also evaluated during dialysis. RESULTS AND CONCLUSIONS: Simultaneous infusion of low molecular weight heparin plus prostacyclin allowed safe and effective anticoagulation without affecting hemodialysis efficiency.

Serum gamma-glutamyl-transpeptidase isoforms in alcoholic liver disease.

gamma-Glutamyltranspeptidase (gamma GT) appears in serum in multiple forms; their significance and clinical utility in hepatobiliary and pancreatic diseases are still a matter of controversy. Electrophoretic separation of the multiple forms of gamma GT on agarose gel was performed in 20 alcoholic patients (six with cirrhosis and 14 with fatty liver) and the results compared with those obtained in 50 healthy volunteers, 43 patients affected with chronic hepatitis C, 36 patients with posthepatitic cirrhosis and in 52 epileptic patients on long-term anti-epileptic medication. Multiple forms of gamma GT were separated into several bands (up to 11), labelled 0a, 0b, 1a, 1b, 2a, 2b, 2c, 3a, 3b, 4a, 4b. In the alcoholic patients nine fractions were detected, and the electrophoretic pattern observed was significantly different from that observed in healthy volunteers and in patients with chronic hepatitis C or posthepatitic cirrhosis. No differences were observed in the electrophoretic patterns in the alcohol abusers and epileptic patients. In alcoholic patients significant differences were observed in the electrophoretic patterns in relation to the degree of liver injury; the electrophoretic patterns in patients with alcohol-related cirrhosis and posthepatitic cirrhosis differed significantly. The separation of multiple forms of gamma GT has high sensitivity and good reproducibility. It may be proposed as a complementary test in the diagnosis of alcoholic liver disease.

Coagulation activation in extracorporeal hemodialysis.

The authors evaluated the behavior of protein C activity, factor X and factor VII coagulant activity and serum lipoprotein(a) before and after dialytic treatment in patients on maintenance hemodialysis. They observed depressed protein C activity that significantly (p < 0.005) increased and became normal immediately after hemodialysis while factor X and factor VII increased (p < 0.01; p < 0.05) despite heparinization together with amount of serum lipoprotein(a). In vitro incubation (30' at 37 degrees C) of uremic and healthy blood showed a decrease in serum lipoprotein(a) concentration. After heparin addition (final concentration 0.5 U/ml) lipoprotein(a) increased in the uremic blood only. The clinical and physiopathological implications of these results are discussed.