Semisynthesis of new sulfated heterorhamnan derivatives obtained from green seaweed Gayralia brasiliensis and evaluation of their anticoagulant activity.

Marine green algae produce sulfated polysaccharides with diverse structures and a wide range of biological activities. This study aimed to enhance the biotechnological potential of sulfated heterorhamnan (Gb1) from Gayralia brasiliensis by chemically modifying it for improved or new biological functions. Using controlled Smith Degradation (GBS) and O-alkylation with 3-chloropropylamine, we synthesized partially water-soluble amine derivatives. GBS modification increase sulfate groups (29.3 to 37.5 %) and α-l-rhamnose units (69.9 to 81.2 mol%), reducing xylose and glucose, compared to Gb1. The backbone featured predominantly 3- and 2-linked α-l-rhamnosyl and 2,3- linked α-l-rhamnosyl units as branching points. Infrared and NMR analyses confirmed the substitution of hydroxyl groups with aminoalkyl groups. The modified compounds, GBS-AHCs and GBS-AHK, exhibited altered anticoagulant properties. GBS-AHCs showed reduced effectiveness in the APTT assay, while GBS-AHK maintained a similar anticoagulant activity level to Gb1 and GBS. Increased nitrogen content and N-alkylation in GBS-AHCs compared to GBS-AHK may explain their structural differences. The chemical modification proposed did not enhance its anticoagulant activity, possibly due to the introduction of amino groups and a positive charge to the polymer. This characteristic presents new opportunities for investigating the potential of these polysaccharides in various biological applications, such as antimicrobial and antitumoral activities.

Semisynthesis and characterization of versatile azide intermediates using sodium alginate and its homopolymeric derivatives as starting material.

Alginate, a polyuronic biopolymer composed of mannuronic and guluronic acid units, contain hydroxyl and carboxyl groups as targeting modification sites to obtain structures with new and/or improved biological properties. The copper-catalyzed azide-alkyne cycloaddition (CuAAC) is a versatile click reaction for polymer functionalization, but it typically requires a "pre-click" modification to introduce azide or alkyne groups. Here, we described a straightforward chemical path to selectively modify alginate carboxyl groups producing versatile azido derivatives through N-acylation using 3-azydopropylamine. The resulting azide-functionalized polysaccharides underwent click chemistry to yield amino derivatives, confirmed by NMR and FTIR analyses. The 1H NMR spectrum reveals a characteristic triazole group signal at 8.15 ppm. The absence of the azide FTIR band for all amino derivatives, previously observed for the N-acylation products, indicated reaction success. Antibacterial and antioxidant assessments revealed that the initial polysaccharide lacks E. coli inhibition, while the click chemistry-derived amine products exhibit growth inhibition at 5.0 mg/mL. Lower molecular weight derivatives demonstrate superior DPPH scavenging ability, particularly amino-derivatives (24-33 % at 1.2 mg/mL). This innovative chemical pathway offers a promising strategy for developing polysaccharide structures with enhanced properties, demonstrating potential applications in various fields.

Pharmacokinetics of oral ciprofloxacin in adult patients: A scoping review.

AIMS: To map the literature on oral ciprofloxacin's pharmacokinetics and its implications for dose adjustments in specific populations. METHODS: A scoping review was performed according to the Cochrane Collaboration and JBI and reported following the PRISMA-ScR. Systematic searches on electronic databases were conducted to integrate the current evidence on ciprofloxacin's pharmacokinetics. The quality of the included studies was assessed using ClinPK's checklist. RESULTS: The search yielded 55 relevant studies. Within the traditional pharmacokinetics studies (n = 46), 86 profiles were examined (72 involving healthy patients and 14 with various clinical conditions). Oral ciprofloxacin's pharmacokinetics were influenced by covariates such as drug interactions (ferrous ions, calcium carbonate, diclofenac and itraconazole), food interactions (calcium-rich foods), elderly populations and renal impairment. Notably, variability in pharmacokinetic parameters existed among subjects, regardless of their health status, underscoring the need for comprehensive population descriptions. Population pharmacokinetic studies (n = 9) identified significant covariates for hospitalized patients, such as creatinine clearance, plasma bicarbonate, estimated glomerular filtration rate, renal replacement therapy, age, sex, total bilirubin, fat-free mass, dietary factors in renal disease, rifampicin for clearance models and body weight for volume of distribution models. Most pharmacokinetic/pharmacodynamic assessments concluded that 1200 mg/day provides a high probability of target attainment for bacteria with minimum inhibitory concentration <0.5 mg L-1 , aiming for an area under the curve for 24 h/minimum inhibitory concentration >125 h. CONCLUSIONS: This study offers a comprehensive overview regarding oral ciprofloxacin's pharmacokinetics across various health conditions. It highlights the complexities of ciprofloxacin's pharmacokinetics, emphasizing the importance of considering multiple factors in dose adjustments.

Morphological study of electrospun chitosan/poly(vinyl alcohol)/glycerol nanofibres for skin care applications.

This study aimed to evaluate the influence of formulation and procedure parameters in obtaining thick and continuous chitosan/PVA/glycerol nanofibres to be applied in skin care. For that, the polymers were characterized by nuclear magnetic resonance, Fourier-transform infrared spectroscopy, and size-exclusion chromatography. After this, 96 chitosan/PVA/glycerol nanofibre scaffolds were prepared by electrospinning method, using factorial designs. The independent variables were crude and pure chitosan, 2 brands of PVA, 2 needle gauges, high and low polymer concentration, high and low glycerol concentration, and final solution with and without ultrafiltration. Morphological analysis was performed by scanning electron microscopy, atomic force microscopy, and confocal microscopy. The best sample (NF67) presented an average thickness of 268.3 nm, uniform distribution, and high yield. It was obtained at a 1:3.5 (crude chitosan: PVA with lower molecular weight, but more hydrolysed) ratio and lower glycerol concentration, suggesting that the degree of hydrolysis of the PVA is more important than its molecular weight for obtaining better quality nanofibres and that the glycerol also makes the electrospinning process difficult. Thus, it was possible to choose parameters that provide scaffolds that could be applied as a matrix extracellular-like material in wound healing.

Advances in microalgal cell wall polysaccharides: a review focused on structure, production, and biological application.

Microalgae have been shown to be useful in several biotechnological fields due to their feasible cultivation and high-value biomolecules production. Several substances of interest produced by microalgae, such as: proteins, lipids, and natural colorants, have already been explored. Based on the continuing demand for new natural molecules, microalgae could also be a valuable source of polysaccharides. Polysaccharides are extremely important in aquaculture, cosmetics, pharmaceutical, and food industries, and have great economic impact worldwide. Despite this, reviews on microalgal polysaccharide production, biological activity, and chemical structure are not abundant. Moreover, techniques of microalgal cultivation, coupled with carbohydrate production, need to be clarified in order to develop forward-looking technologies. The present review provides an overview of the main advances in microalgal cell wall polysaccharide production, as well as their associated potential biological applications and chemical structure. Several studies on future prospects, related to microalgae are presented, highlighting the key challenges in microalgal polysaccharide production.

Experimental Multidisciplinary Approach Based on Compounded Capsule's Quality Evaluation for Pharmacy Undergraduate Courses.

Active learning is common in pharmacy school. However, such learning strategy rarely integrates more than one specific field. Here, we develop a new active multidisciplinary approach centered on compounded capsule's quality evaluation. Captopril capsules were chosen for their important role to control systemic arterial hypertension, a highly prevalent disease. The study design was developed and demonstrated by two undergraduate students. Four compounding pharmacies were selected randomly, and sixty capsules of captopril 25 mg were purchased from each pharmacy at three different periods (12 batches). The capsules were evaluated according to general aspects (visual observation), label information (according to the Brazilian Pharmacopoeia's regulation), weight variation (standard method), and uniformity of dosage units (iodine titration). All batches met the requirements expected for general aspects and one pharmacy did not meet minimum label criteria. Weight variation out of the standard limits was observed for three of the batches evaluated, and five batches were found to be out of the acceptable captopril's dosage. All stages of this activity resulted in important discussions pertaining to the education of pharmacists. The experimental multidisciplinary approach presented a lead to different discussions on several expertise fields and might have a great impact on the formation of future pharmacist. Several topics could be addressed using this activity, such as analytical chemistry, titration, stoichiometry, medicine preparation, pharmacological risks, et h i c a l aspects, and the pharmacist's role to guarantee health.

Stability and Sensory Evaluation of an Innovative Antiaging Formulation Based on Marine Ingredients

Abstract The high consumption of antiaging cosmetics represents an outstanding opportunity for the development of new processes and attractive products in the cosmetic industry. Stability studies and sensory analyses are critical steps in the development process and production chain. Here we present a potential antiaging cosmetic product with innovative sensory characteristics. Caviar extract antioxidant properties were firstly evaluated by the DPPH method since it is an important mechanism against skin aging. Ca-alginate beads containing 2% of caviar extract and 0.2% of black pigment were prepared to obtain spheres similar to caviar. The beads were incorporated in a gel phase (hydroxyethylcellulose 2.5%) containing 3% of dimethylaminoethanol. Stability was evaluated in different storage conditions (sunlight exposure, 5 ± 2 °C, 37 ± 2 °C and r.t.) through the parameters: appearance, color and odor, pH (6-7), density (0.98-1.14 g.mL-1), centrifugation and average size. After approval by the Committee for Ethics in Research (n° 3.503.061), 30 volunteers tested the new formulation and answered a questionnaire. At 2%, caviar extract was able to scavenge 10.9% ± 0.58 of DPPH radical. Formulations showed good stability after 90 days, even considering the average size (7.47 ± 0.41 - 8.4 ± 0.65 mm2). 90% of the sensory test participants reported that they would buy the new product. Therefore, the new product developed demonstrates a promising potential as an attractive cosmetic product.

Development and Evaluation of an Anti-aging Cosmetic Formulation Exploring Antioxidant Potential of Vitis vinifera L.

An important skin aging mechanism is oxidative stress. Reactive oxygen species in excess leads to skin integrity loss and visible changes. Antioxidants are able to prevent reactive oxygen species damage, making their supplementation important to slow down the aging process. We evaluated Vitis vinifera L. extract antioxidant potential to be applied for cosmetic purpose. The sample's thin-layer chromatography profile and antioxidant results indicated a good antioxidant activity. The extract was incorporated into different formulations, and a stability study was conducted with the emulsion chosen. Organoleptic and physicochemical parameters were evaluated, as well as the microbial count. The formulation was found to be in compliance with current standards and has the potential to be further studied and used as an anti-aging cosmetic.

Evaluation of the application of the Diabetes Quality of Life Questionnaire in patients with diabetes mellitus.

Objective Diabetes mellitus (DM) is a chronic disease with great impact on patients' quality of life (QoL). This variable can be measured using reliable, standardized, and validated instruments. The purpose of this study was to evaluate the application and reporting of the Diabetes Quality of Life Measure (DQOL) or the Diabetes Quality of Life for Youths Measure (DQOLY), an adapted version for young patients with DM. Materials and methods A systematic review of interventional and observational studies using the DQOL or DQOLY was performed. Searches were conducted in the electronic databases Medline, Scopus, Web of Science, Lilacs, and SciELO. Results After conducting the searches, 111 studies met the inclusion criteria and were included in the qualitative analysis. Of these, 32 studies were classified as interventional and 79 as observational, with 27,481 patients. The DQOL was applied in 82 studies, the DQOLY in another 27, and two studies used both instruments. DM was classified as type 1 DM in 69 studies and type 2 DM in 35 studies. Six studies included both patients. Improvement in patients' QoL after an intervention was observed in 13 interventional studies. Most of the studies (90%) provide a detailed description of the instrument and 52% the previous validation. The interpretation of the scores obtained varies among the studies, probably due to the differences inherent in cultural validations, translations, and adaptations. Conclusion The application of the instruments in clinical practice must be rigorously standardized and requires an accurate understanding of psychometric and statistical concepts. Arch Endocrinol Metab. 2020;64(1):59-65.

Evaluation of the application of the Diabetes Quality of Life Questionnaire in patients with diabetes mellitus

ABSTRACT Objective Diabetes mellitus (DM) is a chronic disease with great impact on patients' quality of life (QoL). This variable can be measured using reliable, standardized, and validated instruments. The purpose of this study was to evaluate the application and reporting of the Diabetes Quality of Life Measure (DQOL) or the Diabetes Quality of Life for Youths Measure (DQOLY), an adapted version for young patients with DM. Materials and methods A systematic review of interventional and observational studies using the DQOL or DQOLY was performed. Searches were conducted in the electronic databases Medline, Scopus, Web of Science, Lilacs, and SciELO. Results After conducting the searches, 111 studies met the inclusion criteria and were included in the qualitative analysis. Of these, 32 studies were classified as interventional and 79 as observational, with 27,481 patients. The DQOL was applied in 82 studies, the DQOLY in another 27, and two studies used both instruments. DM was classified as type 1 DM in 69 studies and type 2 DM in 35 studies. Six studies included both patients. Improvement in patients' QoL after an intervention was observed in 13 interventional studies. Most of the studies (90%) provide a detailed description of the instrument and 52% the previous validation. The interpretation of the scores obtained varies among the studies, probably due to the differences inherent in cultural validations, translations, and adaptations. Conclusion The application of the instruments in clinical practice must be rigorously standardized and requires an accurate understanding of psychometric and statistical concepts. Arch Endocrinol Metab. 2020;64(1):59-65

Preparation and characterization of a novel antimicrobial film dressing for wound healing application

Antibacterial activity and good mechanical properties are some of the characteristics required for an appropriate film dressing. A novel polymer blend was developed for wound healing application. Twenty-four formulations using the polymers chitosan, poly(vinyl alcohol) and/or ɛ-Polylysine and the plasticizer glycerol were designed using factorial design and then the films were prepared by the casting/solvent evaporation method. Seventeen films were obtained among the twenty-four proposed formulations that were characterized by Field Emission Scanning Electron Microscopy (FE-SEM) and Fourier Transform Infrared Spectroscopy (FTIR). Mechanical properties, such as tensile strength (σ), elongation at break (ɛ) and Young's modulus (Y) as well as antibacterial properties were determined. The best candidate was then further analyzed with regard to porosity, Water Vapor Transmission Rate (WVTR), swelling and cytotoxicity experiments. The results showed a film with semi-occlusive characteristics, good mechanical properties and no toxic. Incorporation of ɛ-Polylysine increased antibacterial activity against gram-negative (Escherichia coli) and gram-positive (Staphylococcus aureus) bacteria

Chemical structure and snake antivenom properties of sulfated agarans obtained from Laurencia dendroidea (Ceramiales, Rhodophyta).

Aqueous and KCl-soluble polysaccharides were extracted from Laurencia dendroidea (Rhodomelaceae, Ceramiales) and their chemical profile was accessed by anion-exchange chromatography, chemical and spectroscopic analyses. The homogeneous agaran DHS-4 (181.3 × 103 g. mol-1, 21.3% of NaSO3) presents A units mostly 2-sulfated (18.9 mol%), nonsubstituted (15.3 mol%) and 6-O-methylated (10.1 mol%), while B units are l-sugars composed predominantly by galactose 6-sulfate precursor units (19.2 mol%) and 3,6-anhydrogalactose (13.8 mol%), besides non-precursor galactose 6-sulfate units bearing d-xylose substituents on C-3 (8.1 mol%). The crude KCl-soluble DHS agaran (20.5% of NaSO3) inhibited proteolysis and hemolysis induced by Lachesis muta and Bothrops jararaca venoms. DHS was able to inhibit up to 75% the L. muta venom hemorrhagic effect and to reduce the lethality displayed by B. jararaca venom, increasing the mice survival time up to 3 times. Therefore, this agaran has high potential to be used as an additional tool to treat snakebite envenomation.

Monitoring of κ-carrageenan depolymerization by capillary electrophoresis and semisynthesis of oligosaccharide alditols.

Different hydrolysis conditions to produce κ-carrageenan oligosaccharide alditols were studied and the depolymerization process monitored by capillary electrophoresis (CE). Semisynthesis, ion-exchange and exclusion chromatography were used to obtain and isolate sulfated di-, tetra- and hexasaccharide alditols, the last being fully characterized for the first time. Those derivatives were used as standards to validate a new quantitative CE analytical method which was used to compare two different partial hydrolysis methodologies: an acid hydrolysis followed by reduction and a one-pot reductive hydrolysis using 4-methylmorpholine borane. The resulting depolymerization profiles were quite different from each other. Optimal hydrolysis conditions to produce high yields of specific sulfated oligosaccharides as well as particular mixtures of oligosaccharide alditols were determined. Moreover, using the novel CE method, we were able to distinguish up to eight different oligosaccharides in the hydrolysate mixtures.

Synthesis and in vitro PDT evaluation of new porphyrins containing meso-epoxymethylaryl cationic groups.

OBJECTIVES: Photodynamic therapy (PDT) is an effective cancer treatment that uses photosensitizers, light, and oxygen to destroy malignant cells. Porphyrins, and in particular the cationic derivatives, are the most investigated photosensitizers for PDT. In this context, it is important to study new methodologies to develop efficient cationic photosensitizers for use in PDT. MATERIALS AND METHODS: New porphyrins bearing cationic epoxymethylaryl groups were synthesized and characterized. Their cellular uptake, intracellular localization, and phototoxicity were evaluated in human HEp2 cells, and compared with their methylated analogs. RESULTS: All cationic porphyrins were efficient generators of singlet oxygen, with quantum yields in the range 0.35-0.61. The two methylated derivatives (3 and 4) accumulated the most within cells at all times investigated, up to 24 hours. Of these two porphyrins, 4 was the most phototoxic to the cells (LD50 = 2.4 µM at 1.5 J/cm2 ); however, porphyrin 3 also showed high phototoxicity (LD50 = 7.4 µM at 1.5 J/cm2 ). The epoxymethyl-containing porphyrins were found to be less phototoxic than the methylated derivatives, with LD50 > 38 µM. The neutral porphyrins showed no phototoxicity up to the 100 µM concentrations investigated, and had the lowest singlet oxygen quantum yields. All cationic porphyrins localized mainly in the cell ER, Golgi apparatus, and lysosomes. CONCLUSION: Our results suggest that cationic methylated porphyrin derivatives are promising PDT photosensitizing agents. The epoxymethyl-containing derivatives showed increased efficacy relative to the neutral analogs, and are good candidates for further investigation. Lasers Surg. Med. 50:566-575, 2018. © 2018 Wiley Periodicals, Inc.

Development and characterization of hyaluronic acid-lysine nanoparticles with potential as innovative dermal filling

ABSTRACT Skin aging causes changes such as wrinkles and flaccidity leading to a large demand for aesthetic procedures, including dermal filling. A key agent in dermal filling is hyaluronic acid (HA), which is a naturally occurring glycosaminoglycan. However, it is a hydrophilic macromolecule that experiences great difficulty in crossing the skin barrier causing most commercial formulations containing it to be injectable, which in turn brings risks since they involve an invasive technique. In that sense, the aim of this study was to develop and characterize nanoparticles obtained from ionic interaction between HA and lysine (Lys) for use as a potential agent of dermal filling for topical application, increasing and improving its applicability and safety. To this end, nanoparticles were obtained by dripping of Lys over HA under magnetic stirring. A nanometric size was confirmed and a suitable surface charge was obtained by zeta potential. Nanoparticles were almost spherical in shape with a smooth surface. Interaction between raw materials for preparing nanoparticles was studied by FTIR and NMR spectroscopy and an ionic interaction was confirmed. These physicochemical features suggest that obtained nanoparticles can be further used as a topical dermal filling.

Kidney failure in the elderly due to hypothyroidism: a case report.

CONTEXT: Hypothyroidism is more prevalent in the elderly and its symptoms can be confused with other changes due to aging. Doctors caring for the elderly need to be attentive to this diagnostic possibility. This case report case is notable not only because it presents a rare complication of hypothyroidism (kidney failure), but also because patients with chronic kidney failure of any etiology may suffer increased renal dysfunction as a result. CASE REPORT: This was a 66-year-old male outpatient with a history of generalized edema over the preceding eight years, with periods of worsening, that was intractable to treatment with diuretics. Physical examination revealed bradycardia (heart rate: 52 bpm), pallor, dry and infiltrated skin, macroglossia, edema in the lower limbs and a palpable thyroid with hard consistency. Laboratory tests showed: creatinine 3.9 mg/dl; urea 95 mg/dl; potassium 6.0 mEq/l; thyroid-stimulating hormone > 100 mUI/ml; triiodothyronine 0.01 ng/dl; free thyroxin 0.01 ng/dl; antithyroglobulin 31 IU/ml (normal values: < 40 IU/ml); antithyroperoxidase 85 IU/ml (normal values: < 15 IU/ml); creatinine clearance 30 ml/min/1.73 m(2); and proteinuria 122 mg/24 h. After five months of treatment with thyroxin (100 mcg/day), the patient returned without any symptoms and presented the following test results: urea 48 mg/dl; creatinine 1.4 mg/dl; creatinine clearance 67 ml/min/1.73 m(2); potassium 4.2 mEq/l; thyroid-stimulating hormone: 20.85 mUI/ml; free thyroxin: 0.71 ng/dl. Hypothyroidism alone can cause renal impairment or worsen renal function in preexisting illnesses. Its treatment can stabilize the clinical condition, or possibly improve it.

Kidney failure in the elderly due to hypothyroidism: a case report / Alteração da função renal no idoso devido ao hipotireoidismo: relato de caso

CONTEXT: Hypothyroidism is more prevalent in the elderly and its symptoms can be confused with other changes due to aging. Doctors caring for the elderly need to be attentive to this diagnostic possibility. This case report case is notable not only because it presents a rare complication of hypothyroidism (kidney failure), but also because patients with chronic kidney failure of any etiology may suffer increased renal dysfunction as a result. CASE REPORT: This was a 66-year-old male outpatient with a history of generalized edema over the preceding eight years, with periods of worsening, that was intractable to treatment with diuretics. Physical examination revealed bradycardia (heart rate: 52 bpm), pallor, dry and infiltrated skin, macroglossia, edema in the lower limbs and a palpable thyroid with hard consistency. Laboratory tests showed: creatinine 3.9 mg/dl; urea 95 mg/dl; potassium 6.0 mEq/l; thyroid-stimulating hormone > 100 mUI/ml; triiodothyronine 0.01 ng/dl; free thyroxin 0.01 ng/dl; antithyroglobulin 31 IU/ml (normal values: < 40 IU/ml); antithyroperoxidase 85 IU/ml (normal values: < 15 IU/ml); creatinine clearance 30 ml/min/1.73 m²; and proteinuria 122 mg/24 h. After five months of treatment with thyroxin (100 mcg/day), the patient returned without any symptoms and presented the following test results: urea 48 mg/dl; creatinine 1.4 mg/dl; creatinine clearance 67 ml/min/1.73 m²; potassium 4.2 mEq/l; thyroid-stimulating hormone: 20.85 mUI/ml; free thyroxin: 0.71 ng/dl. Hypothyroidism alone can cause renal impairment or worsen renal function in preexisting illnesses. Its treatment can stabilize the clinical condition, or possibly improve it.

CONTEXTO: O hipotireoidismo tem uma prevalência elevada em idosos e sua sintomatologia pode ser confundida com alterações próprias do envelhecimento, obrigando o médico que atende o idoso sempre estar atento a essa possibilidade diagnóstica. O relato deste caso chama atenção não somente para uma rara complicação do hipotireoidismo, a insuficiência renal, como para o fato de pacientes portadores de insuficiência renal crônica de qualquer outra etiologia poderem ter piora da disfunção renal devido a esse quadro. RELATO DO CASO: Homem de 66 anos foi atendido em nosso ambulatório com história de edema generalizado há oito anos, com períodos de piora, refratário a tratamento com diuréticos. Ao exame físico encontrava-se bradicárdico (freqüência cardíaca 52 bpm), hipocorado; pele ressecada e infiltrada; macroglossia; edema de membros inferiores; tireóide palpável e de consistência endurecida. Exames laboratoriais mostraram: creatinina 3,9 mg/dl; uréia 95 mg/dl; potássio 6,0 mEq/l; hormônio estimulante da tireóide, TSH > 100 mUI/ml; T3 0,01 ng/dl; T4 0,01 ng/dl; anti-tireoglobulina 31 UI/ml (< 40 UI/ml); anti-tiroperoxidase 85 UI/ml (< 15 UI/ml); clearence de creatinina 30 ml/min/1,73 m²; proteinúria 122 mg/24 h. Após cinco meses de tratamento com tiroxina 100 mcg/dia o paciente retornou ao ambulatório assintomático, apresentando os seguintes exames: uréia 48 mg/dl; creatinina 1,4 mg/dl; clearence de creatinina 67 ml/min/1,73 m²; potássio 4,2 mEq/l; TSH 20,85 mUI/ml; T4 livre 0,71 ng/dl. CONCLUSÃO: O hipotireoidismo per se pode levar a insuficiência renal ou piorar a função renal em doenças preexistentes. Seu tratamento pode reverter essa condição clínica ou, pelo menos, melhorá-la.