Evaluating total nitrogen and phosphorous concentrations in a watershed impacted by diverse anthropic activities in a developing country.

This research aims to identify critical contamination points by nutrients, their possible origin (point and nonpoint sources), their spatial distribution, and possible attenuation by natural and anthropogenic processes. The study area is the Velhas River Basin, located in the Southeast Region of Brazil (17.0°-20.5° S; 43.5°-45.0°W). A historical series of water quality monitoring, land cover map, demographic and agricultural censuses, sewage treatment diagnostics, and local hydrographic networks were used to achieve the objectives. In addition, the regions were divided into incremental areas, enabling individualized analyses of each sub-basin. Descriptive statistics, seasonality, categorized data tests, agglomerative hierarchical cluster analysis, and principal component analysis were used. There was a significant contribution of nutrients in the most important urban agglomeration of the basin, resulting in peak concentrations measured at that place. Although the values were reduced by the mouth (650 km), the percentage of legislation violations remained high. The effects of punctual contamination were intensified by the low percentage of treated sewage in the basin, the absence of adequate treatment technologies to remove nutrients, and the disorderly urbanization. Furthermore, it was estimated that the nutrient load from animal husbandry is approximately 75% of the load from domestic effluents due to the high number of cattle in the basin and the low percentage of forests.

In vivo evaluation of analgesic and anti-inflammatory activity of hydroalcoholic extracts from Handroanthus impetiginosus and their chemical composition by UPLC/MS analysis.

This study demonstrates in vivo analgesic and anti-inflammatory properties of hydroalcoholic extracts of leaves, bark and flowers from the Handroanthus impetiginosus (Bignoniaceae) plant, recognized as 'Ipê roxo' in Brazil. The extracts were evaluated in male Swiss albino mice via oral administration. Moreover, results of the in vivo paw oedema test induced by carrageenan revealed that extracts of leaves and bark displayed relevant anti-inflammatory activity potential at the dosage of 100 mg/kg, 300 mg/kg, and 500 mg/kg. Likewise, the results obtained for leaves and flowers extracts suggested potent analgesic action in the conventional hot plate test. UPLC/MS analysis of the hydroalcoholic extracts samples identified metabolites belonging to several classes, mainly naphthoquinones and iridoids derivatives as well as flavonoids. Thus, the obtained results indicate that the extracts of H. impetiginosus plant parts could be considered as a complementary herbal medicine for the treatment of pain and inflammation disorders.

Short communication: Utilisation of n-alkanes to estimate feed intake in horses fed known amounts of a labelled concentrate supplement.

The assessment of feed intake in stabled horses is a difficult task to accomplish. Faecal markers, namely n-alkanes, have been used successfully for the estimation of this important nutritional parameter. This usually involves the dosing of synthetic n-alkanes via different matrices, a laborious task that may also influence the animal normal foraging behaviour. An experiment was conducted to evaluate a relative simple methodology to quantify feed intake in horses, based on the provision of measured amounts of a concentrate supplement labelled with beeswax and the utilisation of n-alkanes as faecal markers. Four Lusitano horses were used in three consecutive experimental periods. Animals were fed on cereal straw and different proportions of a previously prepared beeswax-labelled concentrate supplement (BLCS; 0.05, 0.10 and 0.20, DM basis). Beeswax labelling was performed to provide a distinct n-alkane profile for the concentrate feed. Prior to feed intake calculations, proportions of labelled concentrate supplement in the diets were estimated using n-alkanes C25 to C33 by least-square optimisation procedures. Results showed that the beeswax labelling resulted in high n-alkane concentrations in the concentrate feed, especially for the odd-chain n-alkanes. Estimates of diet composition did not differ from the measured values, except for the diet with highest BLCS incorporation, with an underestimation of 10%. DM intake was accurately estimated by the "labelled supplement method" in all diets. However, for the lowest BLCS incorporation, DM intake was underestimated by 16% whereas for the higher levels of BLCS in the diet, measured and estimated DM intake values were almost identical with a slight overestimation of only 0.7 and 0.2% (10 and 20% of BLCS, respectively). Results indicate that both diet composition and feed intake can be accurately estimated in horses using the "labelled supplement method", even when very low levels of the labelled concentrate supplement are included in the animals' diet. This method eliminates the need for daily dosing with external synthetic markers, providing advantages in terms of minimising animal management and interference with their normal foraging behaviour.

Cuidados de enfermagem na atenção primária à pessoa com úlcera varicosa: relato de caso / Nursing care in primary care for people with varicose ulcer: case report / Atención de enfermería en atención primaria a personas con úlcera variciosa: reporte de caso

Objetivo: Descrever os cuidados de enfermagem aplicados a um paciente com lesão venosa em membros inferiores na Atenção Primária à Saúde. Métodos:Pesquisa exploratória-descritiva, do tipo estudo de caso, que apresenta o acompanhamentode um paciente, sexo masculino, atendido em uma Unidade Básica de Saúde organizada no modelo de Estratégia Saúde da Família, pertencente a um município de Minas Gerais, no período de junho a dezembro de 2020. Resultados:Considerando as condições de saúdeapresentadas pelo paciente na primeira consulta de enfermagem, foi traçado um plano de cuidado assistencial sistematizado, visando atender as necessidades de saúde reportadas, com foco nas mudanças de estilo de vida, protagonismo e autonomia do paciente, que positivamente ao longo de toda assistência, permitiu reduzir as complicações vasculares e consequentemente evoluir para a cicatrização das lesões ao longo do acompanhamento. Considerações finais:A abordagem do paciente com úlcera varicosa na Atenção Primária à Saúde, deve ser para além da realização do curativo. A cicatrização das lesões e a prevenção de recidivas está relacionada a oferta de uma assistência de enfermagem integral e holística, com coordenação do cuidado e participação de toda a equipe multidisciplinar.

Objective: To describe the nursing care applied to a patient with venous injury in the lower limbs in PrimaryHealth Care. Methods:Exploratory-descriptive research, of the case study type, which presents the follow-up of a male patient, assisted in a Basic Health Unit organized in the Family Health Strategy model, belonging to a municipality of Minas Gerais, from June to December 2020. Results:Considering the health conditions presented by the patient in the first nursing consultation, a plan was drawn up of systematized care, aiming to meet the reported health needs, with a focus on changes in lifestyle, protagonism and patient autonomy, which positively throughout the entire care, allowed to reduce vascular complications and consequently evolve to the healing of lesions over time.throughout the follow-up. Final considerations: The approach of the patient with varicose ulcer in Primary Health Care must go beyond the dressing. Wound healing and relapse prevention are related to the provision of comprehensive and holistic nursing care, with care coordination and participation of the entire multidisciplinary team.

Objetivo: Describir los cuidados de enfermería aplicados a un paciente con lesión venosa en miembros inferiores en la Atención Primaria de Salud. Métodos:Investigación exploratoria-descriptiva, del tipo estudio de caso, que presenta el seguimiento de un paciente del sexo masculino, atendido en una Unidad Básica de Salud organizada en el modelo Estrategia de Salud de la Familia, perteneciente a un municipio de Minas Gerais, en el período de Junio a diciembre de 2020. Resultados:Considerando las condiciones de salud presentadas por el paciente en la primera consulta de enfermería, se elaboró un plan de cuidados sistematizado, con el objetivo de atender las necesidades de salud relatadas, con foco en cambios de estilo de vida, protagonismo y autonomía del paciente, que positivamente a lo largo toda la asistencia, permitió la reducción de las complicaciones vasculares y consecuentemente avanzar a la cicatrización de las lesiones durante el seguimiento. Consideraciones finales:El abordaje del paciente con úlcera varicosa en Atención Primaria de Salud debe ir más allá del apósito. La cicatrización de heridas y la prevención de recaídas están relacionadas con la prestación de cuidados de enfermería integrales y holísticos, con coordinación asistencial y participación de todo el equipo multidisciplinario.

In vivo study of anti-inflammatory and antinociceptive activities of Copaifera pubiflora Benth oleoresin.

Copaifera pubiflora Benth oleoresin (CPO) is used as an anti-inflammatory, wound healing, and antimicrobial. This paper reports the cytotoxic, anti-inflammatory, and antinociceptive activities of CPO. CPO (10 mg/kg) did not affect locomotor capacity in the open-field and rotarod tests and was not cytotoxic to CHO-k1, THP-1, and L929 cell lines. It was active in the formalin test at 3 mg/kg by 86 ± 3% and 96 ± 3%, respectively, for the first and second phases. At 10 mg/kg, CPO inhibited 90 ± 7%, the pain in the mechanical hyperalgesia test. In the tail-flick test, CPO at 3 mg/kg affected the tail-flick latencies in mice by 77 ± 20%, which in combination with naloxone was only partially reduced. At 3 mg/kg CPO inhibited 80 ± 12% the carrageenan-induced paw edema, and at 3 mg/kg it reduced by 91 ± 5% the nociception on acetic acid-induced abdominal writhing. Therefore, CPO possesses anti-inflammatory and antinociceptive activities.

Chemical study of Adenocalymma axillarum crude leaf extract and isolated compounds

Abstract Adenocalymma axillarum (K.Schum.) L.G. Lohmann is a liana belonging to the family Bignoniaceae. In traditional medicine, the genus Adenocalymma is used to treat fever, skin ailments, and body, joint, and facial muscle pains, and it is also applied as cosmetic. Biological assays conducted with the A. axillarum crude leaf ethanol extract have indicated leishmanicidal activity and absence of cytotoxicity. This study aimed to analyze the A. axillarum leaf ethanol crude extract by high-performance liquid chromatography-high-resolution mass spectrometry- diode array detector (HPLC-HRMS-DAD) and to evaluate the leishmanicidal and cytotoxic activities of this crude extract, its fractions, and isolated compounds. HPLC-HRMS-DAD analysis of this extract revealed that it consisted mainly of flavonoids, with nine major compounds. Extract purification yielded 4-hydroxy-N-methylproline, 6-β-hydroxyipolamiide, quercetin-3-O-robinobioside, hyperin, isorhamnetin-3-O-robinobioside, and 3'-O-methylhyperin, which were identified by Nuclear Magnetic Resonance. The isolated compounds were inactive against Leishmania amazonensis promastigotes and human lung fibroblast cells.

Antinociceptive and anti-inflammatory activities of Copaifera pubiflora Benth oleoresin and its major metabolite ent-hardwickiic acid.

ETHNOPHARMACOLOGICAL RELEVANCE: Copaifera species folkloric names are "copaíbas, copaibeiras, copaívas or oil stick", which are widely used in Brazilian folk medicine. Among all ethnopharmacological applications described for Copaifera spp oleoresins, their anti-inflammatory effect stands out. However, the knowledge of anti-inflammatory and antinociceptive properties of Copaifera pubiflora Benth is scarce. AIM OF THE STUDY: To investigate the cytotoxic, anti-inflammatory, and antinociceptive activities of C. pubiflora oleoresin (CPO), and its major compound ent-hardwickiic acid (HA). MATERIAL AND METHODS: The phosphatase assay was used to evaluate the cytotoxicity of CPO and HA in three different cell lines. CPO and HA doses of 1, 3, and 10 mg/kg were employed in the biological assays. The assessment of motor activity was performed using open-field and rotarod tests. Anti-inflammatory activity of CPO and HA was assessed through luciferase assay, measurement of INF-γ, IL-1ß, IL-6, IL-10, and TNF-α in a multi-spot system with the immortalized cell line THP-1, zymosan-induced arthritis, and carrageenan-induced paw edema. Acetic acid-induced abdominal writhing and formalin tests were undertaken to evaluate the antinociceptive potential of CPO and HA. In addition, the evaluation using carrageenan was performed to investigate the effect of CPO in pain intensity to a mechanical stimulus (mechanical hyperalgesia), using the von Frey filaments. A tail-flick test was used to evaluate possible central CPO and HA actions. RESULTS: In the cytotoxicity evaluation, CPO and HA were not cytotoxic to the cell lines tested. CPO and HA (10 mg/kg) did not affect animals' locomotor capacity in both open-field and rotarod tests. In the luciferase assay, CPO and HA significantly reduced luciferase activity (p < 0.05). This reduction indicates a decrease in NF-κB activity. HA and CPO decreased INF-γ, IL-1ß, IL-6, IL-10, and TNF-α at 24 and 72 h in the multi-spot system. In zymosan-induced arthritis, CPO and HA decreased the number of neutrophils in the joint of arthritic mice and the number of total leukocytes (p < 0.05). In experimental arthritis HA significantly decreased joint swelling (p < 0.05). CPO and HA also increased the mechanical threshold during experimental arthritis. HA and CPO significantly inhibited the carrageenan-induced paw edema, being the doses of 10 mg/kg the most effective, registering maximum inhibitions of 58 ± 8% and 76 ± 6% respectively, p < 0.05. CPO and HA reduced the nociceptive behavior in both phases of formalin at all tested doses. The highest doses tested displayed inhibitions of 87 ± 1% and 72 ± 4%, respectively, p < 0.001, in the first phase, and 87 ± 1% and 81 ± 2%, respectively, p < 0.001, in the second phase. Oral treatment of CPO and HA (1, 3, 10 mg/kg) significantly reduced the nociceptive response in acetic acid-induced abdominal writhings, and the 10 mg/kg dose was the most effective with maximum inhibitions of 86 ± 2% and 82 ± 1%, respectively, p < 0.001. Both HA and CPO significantly decreased the intensity of mechanical inflammatory hyper-nociception on carrageenan-induced hyperalgesia at all tested doses, and 10 mg/kg was the most effective dose with maximum inhibitions of 73 ± 5% and 74 ± 7%, respectively, p < 0.05.CPO increased the tail-flick latencies in mice, and concomitant administration of naloxone partially reduced its effect. CONCLUSIONS: CPO and HA may inhibit the production of inflammatory cytokines by suppressing the NF-κB signaling pathway, resulting in anti-inflammatory and antinociceptive activities.

In vitro anthelmintic activity of the crude hydroalcoholic extract of Piper cubeba fruits and isolated natural products against gastrointestinal nematodes in sheep.

This study describes the in vitro anthelmintic activity of a hydroalcoholic extract from the fruit of Piper cubeba and its major isolated components against the eggs and larvae of gastrointestinal nematodes obtained from naturally-infected ovines. In vitro anthelmintic activity was evaluated using the egg hatch test (EHT), larval development test (LDT) and L3 migration inhibition test (LMT). The extract showed ovicidal and larvicidal activity, with an EC50 of 200 µg/mL and 83.00 µg/mL in the EHT and LDT, respectively. The extract inhibited 100% of larval migration at the lowest tested concentration (95 µg/mL). The crude extract was purified using successive silica gel chromatographic columns, which revealed the lignans hinokinin, cubebin and dihydrocubebin as the major compounds that were present, which were then used in in vitro tests. Cubebin, dihydrocubebin and hinokinin showed higher activity than the crude extract, with an EC50 for ovicidal activity of 150.00 µg/mL, 186.70 µg/mL and 68.38 µg/mL, respectively. In the LDT, cubebin presented an EC50 of 14.89 µg/mL and dihydrocubebin of 30.75 µg/mL. Hinokinin inhibited 100% the larval development at all concentrations evaluated. In the LMT, dihydrocubebin inhibited 100% the larval migration in all concentrations evaluated while cubebin and hinokinin showed EC50 values of 0.89 µg/mL and 0.34 µg/mL, respectively. P. cubeba extract is rich in several classes of active compounds, but here we demonstrate that the described anthelmintic activity may be related to the presence of these lignans, which are present in larger concentrations than other components of the extract. Our results demonstrate for first time the anthelmintic activity against gastrointestinal nematodes in sheep for this class of special metabolites that are present in P. cubeba fruit. However, future detailed studies are needed to evaluate the effectiveness of P. cubeba fruits extract and active lignans in in vivo tests.

Taste disorders following cancer treatment: report of a case series.

PURPOSE: To present the findings of combined oral assessment and gustometry testing of a series of head and neck and hematologic malignancies in patients with self-reported taste change after cytotoxic therapies. METHODS: Patients with acute myeloid leukemia (AML), multiple myeloma (MM), and head and neck cancer (HNC) were evaluated for taste function. Chemical gustometry was conducted assessing chemosensory qualities that included sweet, sour, salty, bitter, umami, and spicy. NCI Common Terminology Criteria for Adverse Events (CTCAE) 4.0 and the Scale of Subjective Total Taste Acuity (STTA) were used to describe taste symptoms. Saliva flow rates were measured to determine the presence of hyposalivation. Patients were provided treatment trials for taste dysfunction, including zinc supplements, or medications that included clonazepam, megestrol acetate, and the cannabinoid dronabinol. RESULTS: According to STTA, hematology cases reported the incidence of grades 2 and 3 taste disturbances as 60% and 40%, respectively. For HNC patients, the incidence of grades 2 and 3 was 44% each. Gustometry tests confirmed dysgeusia in all patients evaluated. In the hematology group, 80% of patients exhibited a decrease in sweet taste perception, and no patients correctly identified umami taste. In the HNC group, most patients could not identify salt taste, 66% of patients reported "no sensation" with spicy taste, bitter taste was reduced in some, and increased or altered in others, while only one patient could identify umami taste. In the hematologic and HNC patient groups, 80% and 66% reported grade 2 dry mouth, respectively, according to CTCAE 4.0. After treatment for taste dysfunction, 71% of all patients in the present study reported improvements in taste function. CONCLUSIONS: Persisting dysgeusia in cancer survivors may be assessed by patient report and taste testing. The taste most affected in our patients was umami. Treatment trials with current interventions for dysgeusia appeared effective and should be considered in cancer survivors. Understanding taste and flavor function during and following cancer treatment is important in developing rational prospective preventive and interventional strategies.

Evaluation of Lignans from Piper cubeba against Schistosoma mansoni Adult Worms: A Combined Experimental and Theoretical Study.

Six dibenzylbutyrolactonic lignans ((-)-hinokinin (1), (-)-cubebin (2), (-)-yatein (3), (-)-5-methoxyyatein (4), dihydrocubebin (5) and dihydroclusin (6)) were isolated from Piper cubeba seed extract and evaluated against Schistosoma mansoni. All lignans, except 5, were able to separate the adult worm pairs and reduce the egg numbers during 24 h of incubation. Lignans 1, 3 and 4 (containing a lactone ring) were the most efficient concerning antiparasitary activity. Comparing structures 3 and 4, the presence of the methoxy group at position 5 appears to be important for this activity. Considering 1 and 3, it is possible to see that the substitution pattern change (methylenedioxy or methoxy groups) in positions 3' and 4' alter the biological response, with 1 being the second most active compound. Computational calculations suggest that the activity of compound 4 can be correlated with the largest lipophilicity value.

The Effect of Auricular and Systemic Acupuncture on the Electromyographic Activity of the Trapezius Muscle with Trigger Points-A Pilot Study.

The purpose of this study was to analyze and compare intra and intergroup the immediate effect of the auricular and LR8 systemic acupuncture on the electromyographic activity of the trapezius with the trigger points. This is an experimental clinical trial; 40 people were split in 4 distinct groups (n = 10): GI mustard seed application in the auricular acupoint; GII bilateral needle application in the LR8 acupoint; GIII combination of the techniques; GIV/Control Group mustard seed application in an acupoint not linked to the muscle tension. The EMG was used to assess the muscle contraction for 5 seconds during the resting time and during the isometric contraction time. The EMG signal was first collect without the acupuncture intervention; then both techniques were applied for 5 minutes; and the EMG was collected again right after these applications. The Shapiro-Wilk test was used, the t test was paired with the Wilcoxon test to the intragroup comparison; One-way analysis of variance test for intergroup comparison. There was no statistical difference in the intragroup comparison for the groups. The same happened to the intergroup comparison before and after application. Systemic and auricular acupuncture did not promote immediate changes in the EMG activity of the trapezius muscle in individuals with MTrPs.

Ecotoxicological and microbiological assessment of sewage sludge associated with sugarcane bagasse.

Sewage sludge (SS) obtained after sewage treatment process may contain several toxic substances. Bioremediation can decrease the toxicity of the sludge, mainly when it is associated with stimulant agents, such as sugarcane bagasse (B). Samples of pure SS (SSP); SS+B; SS+Soil; and SS+B+Soil were bioremediated for 1, 3, and 6 months (T1, T2, and T3, respectively). After each period, the cytotoxic, genotoxic, and mutagenic potentials of the solid samples and their respective aqueous extracts (aqueous eluate and percolate water) were evaluated by the Allium cepa test. A microbiological analysis of the samples was also performed after each period tested. All solid samples of SS+B (in T1, T2, and T3) and the solid sample of SSP (treatment T3) showed a significant decrease of cell division (cytotoxic effects). The aqueous eluate extracts of SS+B (T1 and T3) and SSP (T2 and T3) induced cytotoxic effect. The solid sample of SS+B (T2 and T3) and aqueous extracts of SSP (T1) were genotoxic, indicating a harmful effect of SS on A. cepa, even after 6 months of bioremediation. There was an alternation in the microbial community both in diversity and in abundance, with the predominance of nonfermenting gram-negative bacilli. The tested bioremediation periods were not sufficient for the complete detoxification of SS, and the use of B did not seem to contribute to the degradation of the pollutants to inert compounds. These data emphasize that a specific relationship should exist between the sludge characteristic and the biostimulating agent used to promote a more efficient bioremediation. These results suggest the necessity to study longer periods of biodegradation and the use of other decomposing agents for greater safety and sustainability for the agricultural use of this residue.

Non-clinical studies in the process of new drug development - Part II: Good laboratory practice, metabolism, pharmacokinetics, safety and dose translation to clinical studies.

The process of drug development involves non-clinical and clinical studies. Non-clinical studies are conducted using different protocols including animal studies, which mostly follow the Good Laboratory Practice (GLP) regulations. During the early pre-clinical development process, also known as Go/No-Go decision, a drug candidate needs to pass through several steps, such as determination of drug availability (studies on pharmacokinetics), absorption, distribution, metabolism and elimination (ADME) and preliminary studies that aim to investigate the candidate safety including genotoxicity, mutagenicity, safety pharmacology and general toxicology. These preliminary studies generally do not need to comply with GLP regulations. These studies aim at investigating the drug safety to obtain the first information about its tolerability in different systems that are relevant for further decisions. There are, however, other studies that should be performed according to GLP standards and are mandatory for the safe exposure to humans, such as repeated dose toxicity, genotoxicity and safety pharmacology. These studies must be conducted before the Investigational New Drug (IND) application. The package of non-clinical studies should cover all information needed for the safe transposition of drugs from animals to humans, generally based on the non-observed adverse effect level (NOAEL) obtained from general toxicity studies. After IND approval, other GLP experiments for the evaluation of chronic toxicity, reproductive and developmental toxicity, carcinogenicity and genotoxicity, are carried out during the clinical phase of development. However, the necessity of performing such studies depends on the new drug clinical application purpose.

Schistosomicidal Activity of Alkyl-phenols from the Cashew Anacardium occidentale against Schistosoma mansoni Adult Worms.

Bioassay-guided study of the ethanol extract from the cashew Anacardium occidentale furnished cardol triene (1), cardol diene (2), anacardic acid triene (3), cardol monoene (4), anacardic acid diene (5), 2-methylcardol triene (6), and 2-methylcardol diene (7). 1D- and 2D-NMR experiments and HRMS analysis confirmed the structures of compounds 1-7. Compounds 2 and 7 were active against Schistosoma mansoni adult worms in vitro, with LC50 values of 32.2 and 14.5 µM and selectivity indices of 6.1 and 21.2, respectively. Scanning electron microscopy of the tegument of male worms in the presence of compound 7 at 25 µM after 24 h of incubation showed severe damage as well as peeling and reduction in the number of spine tubercles. Transmission electron microscopy analyses revealed swollen mitochondrial membrane, vacuoles, and altered tegument in worms incubated with compound 2 (25 µM after 24 h). Worms incubated with compound 7 (25 µM after 24 h) had lysed interstitial tissue, degenerated mitochondria, and drastically altered tegument. Together, the results indicated that compound 7 presents promising in vitro schistosomicidal activity.

Non-clinical studies required for new drug development - Part I: early in silico and in vitro studies, new target discovery and validation, proof of principles and robustness of animal studies.

This review presents a historical overview of drug discovery and the non-clinical stages of the drug development process, from initial target identification and validation, through in silico assays and high throughput screening (HTS), identification of leader molecules and their optimization, the selection of a candidate substance for clinical development, and the use of animal models during the early studies of proof-of-concept (or principle). This report also discusses the relevance of validated and predictive animal models selection, as well as the correct use of animal tests concerning the experimental design, execution and interpretation, which affect the reproducibility, quality and reliability of non-clinical studies necessary to translate to and support clinical studies. Collectively, improving these aspects will certainly contribute to the robustness of both scientific publications and the translation of new substances to clinical development.

Activity of the Lichen Usnea steineri and its Major Metabolites against Gram-positive, Multidrug-resistant Bacteria.

The antimicrobial activity and possible synergistic effects of extracts and compounds isolated from Usnea steineri were evaluated against four resistant bacterial species. A phytochemical study of the acetone extract of U. steineri resulted in the isolation and characterization of difractaic acid and (+)-usnic acid as the main compounds. The acetone extract showed strong activity (less than 10 µg/mL) against resistant strains of Staphylococcus epidermidis and Enterococcus faecalis, and (+)-usnic acid exhibited strong activity against S. epidermidis (MIC 3.12 µg/mL), S. aureus and S. haemnolyticus (MIC 12.5 µg/mL). Combinations of penicillin and tetracycline with (+)-usnic acid did not show any synergistic antimicrobial effects. Difractaic acid was inactive. Our results showed that the acetone extract of U. steineri possesses significant in vitro antimicrobial activity, which is likely related to the presence of (+)-usnic acid.

Oral physiology, nutrition and quality of life in diabetic patients associated or not with hypertension and beta-blockers therapy.

The relationship between type 2 diabetes oral physiology, nutritional intake and quality of life has not been fully elucidated. We assessed the impact of type 2 diabetes - exclusive or associated with hypertension with beta-blockers treatment - on oral physiology, mastication, nutrition and quality of life. This cross-sectional study was performed with 78 complete dentate subjects (15 natural teeth and six masticatory units minimum; without removable or fixed prostheses), divided into three groups: diabetics (DM) (n = 20; 45·4 ± 9·5 years), diabetics with hypertension and receiving beta-blockers treatment (DMH) (n = 19; 41·1 ± 5·1 years) and controls (n = 39; 44·5 ± 11·7 years) matched for gender, age and socioeconomic status. Blood glucose, masticatory performance, swallowing threshold, taste, food intake, stimulated and unstimulated salivary flow, pH and buffering capacity of saliva were assessed. Glycemia was higher in DM than in controls (P < 0·01). No differences were observed between DM and controls for nutrition and quality of life. Both stimulated and unstimulated salivary flow rate were lower in DMH (P < 0·01), which also presented the lowest number of teeth and masticatory units (P < 0·0001), and reduction in the number of chewing cycles (P < 0·01). Controls showed lower Decayed Missing Filled Teeth index (DMFT) scores in comparison with DMH (P = 0·021). Masticatory performance and saliva buffering capacity were similar among groups. Exclusive type 2 diabetes did not alter oral physiology, nutrition or quality of life. However, when hypertension and beta-blockers treatment were associated with diabetes, the salivary flow rate, chewing cycles and number of teeth decreased.

Clinical effects of an avocado-soybean unsaponifiable extract on arthralgia and osteoarthritis of the temporomandibular joint: preliminary study.

The aim of the present preliminary study was to investigate the effectiveness of an avocado-soybean unsaponifiable extract (ASU) in patients with arthralgia and osteoarthritis of the temporomandibular joint (TMJ). A randomized, double-blind, placebo-controlled trial was carried out. Fourteen women diagnosed with arthralgia and osteoarthritis of the TMJ using the Research Diagnostic Criteria for Temporomandibular Disorders were included in the statistical analysis. The women were allocated randomly to two groups: ASU group and placebo group. Pain was measured using a visual analogue scale and pressure algometer. Mandibular function was evaluated through measurement of mandibular movements. Quality of life was measured using the Oral Health Impact Profile (OHIP-14). The medication (ASU capsules or placebo capsules) was used for 4 months and the total follow-up was 6 months. Those taking the ASU extract had a decrease in pain symptoms and an improvement in quality of life. Moreover, a significant reduction in the use of rescue medication was found in the ASU group compared to the placebo group. This preliminary study provides strong evidence of the effectiveness of an avocado-soybean unsaponifiable extract in patients with degenerative joint diseases and arthralgia in the TMJ. Further studies with larger samples should be performed.

Non-clinical studies in the process of new drug development - Part II: Good laboratory practice, metabolism, pharmacokinetics, safety and dose translation to clinical studies

The process of drug development involves non-clinical and clinical studies. Non-clinical studies are conducted using different protocols including animal studies, which mostly follow the Good Laboratory Practice (GLP) regulations. During the early pre-clinical development process, also known as Go/No-Go decision, a drug candidate needs to pass through several steps, such as determination of drug availability (studies on pharmacokinetics), absorption, distribution, metabolism and elimination (ADME) and preliminary studies that aim to investigate the candidate safety including genotoxicity, mutagenicity, safety pharmacology and general toxicology. These preliminary studies generally do not need to comply with GLP regulations. These studies aim at investigating the drug safety to obtain the first information about its tolerability in different systems that are relevant for further decisions. There are, however, other studies that should be performed according to GLP standards and are mandatory for the safe exposure to humans, such as repeated dose toxicity, genotoxicity and safety pharmacology. These studies must be conducted before the Investigational New Drug (IND) application. The package of non-clinical studies should cover all information needed for the safe transposition of drugs from animals to humans, generally based on the non-observed adverse effect level (NOAEL) obtained from general toxicity studies. After IND approval, other GLP experiments for the evaluation of chronic toxicity, reproductive and developmental toxicity, carcinogenicity and genotoxicity, are carried out during the clinical phase of development. However, the necessity of performing such studies depends on the new drug clinical application purpose.

Efetividade da hidroterapia e da cinesioterapia na reabilitação de idosos com histórico de quedas / Effectiveness of hydrotherapy and kinesiotherapy in elderly patients with history of falls

A fisioterapia tem um papel fundamental na reabilitação funcional de idosos com histórico de quedas. O objetivo deste estudo foi avaliar a efetividade do protocolo de hidroterapia e cinesioterapia no equilíbrio, na agilidade e na estatura em idosos que costumam cair. Foram avaliados 14 idosos por meio de estadiômetro, escala de equilíbrio de Berg e Timed Up & Go. Os idosos foram alocados em dois grupos: G1, tratados com hidroterapia, e G2, tratados com cinesioterapia. O protocolo teve duração de 2 meses, sendo duas vezes por semana e sessões de 40 minutos, totalizando 16 atendimentos. Após 16 sessões, os participantes foram reavaliados. Os dados foram analisados estatisticamente pelos testes Kruskal-Wallis e Wilcox-Mann-Whitney. Comparando-se os dois grupos, verificou-se que ambos os grupos apresentaram maior pontuação na escala de equilíbrio de Berg, menor tempo na realização do Timed Up & Go e uma tendência a significância na estatura corporal após a aplicação do protocolo No entanto, não houve diferenças estatisticamente entre os grupos. Pode-se concluir que a hidroterapia e a cinesioterapia são efetivas para a melhora do equilíbrio e agilidade dos participantes, amenizando o declínio da capacidade funcional inerente ao envelhecimento. (AU)

Effectiveness of hydrotherapy and kinesiotherapy in elderly patients with history of falls The functional rehabilitation of elderly fallers is an objective of physical therapy. The aim of this study was to evaluate the effectiveness of hydrotherapy and kinesiotherapy protocols in balance, agility and height in falling elder ones. We evaluated 14 elderly patients with history of falls. The outcome measures were the Berg Balance Scale score, Timed up & go and height. The participants were randomly divided in two groups: G1, treated with hydrotherapy, G2 treated with kinesiotherapy. The experimental intervention was a 40-minute session per day, 2 days per week for 2 months. Data were statistically analyzed by the Kruskal-Wallis and Mann-Whitney-Wilcox tests. Comparing the two groups, it was found that both groups increased Berg Balance Scale and decreased Timed Up & Go and there is a significance in stature after the implementation of the protocol. However, there were no statistical differences between the two groups. In conclusion, this study suggests hydrotherapy and kinesiotherapy are effective for improving balance and agility in the sample of participants, reducing the decline in functional capacity inherent to the aging.(AU)