Cinchona bark and quinine in the Portuguese official pharmacopoeias (1794-2001).

Cinchona bark (bark from plants of the genus Cinchona with antimalarial activity) and its alkaloid quinine were widely used to treat intermittent fevers. This paper aims to quantitatively analyze the presence of Cinchona bark, quinine and other Cinchona bark-derived substances in the Portuguese official pharmacopoeias published between 1794 and 2001. The analysis showed that the Pharmacopêa Portugueza (1876) is the Portuguese official pharmacopeia with the highest percentage of medicines containing Cinchona bark (2.61%). The Farmacopeia Portuguesa IV (1935) is the official pharmacopeia with the highest percentage of quinine-containing medicines (2.34%). Medicines made from Cinchona bark are present in the Portuguese official pharmacopoeias until the Farmacopeia Portuguesa IV (1946). Medicines made from quinine have been present in Portuguese official pharmacopoeias since the Codigo Pharmaceutico Lusitano (1835).

The influence of German science on Cinchona and quinine research in Portugal in the second half of the 19th century.

This paper examines the contribution of three Portuguese scientists to Cinchona cultivation in the former Portuguese colonies in the second half of the 19th century, while discussing the importance of their studies in Germany to their professional lives. Portuguese pharmaceutical, medical, and botanical literature from the 19 th and 20 th century was reviewed, as well as books and articles regarding the history of pharmacy and medicine in Portugal. Cinchona bark, source of the antimalarial alkaloid quinine, is obtained from a South American plant, and was an important commodity in the 19th century. Many European nations (including Portugal) tried to acclimatize and cultivate Cinchona plants in their colonies. Pharmacist Joaquim dos Santos e Silva (1842-1906) performed chemical analysis of Cinchona bark samples from the Portuguese colonies in Africa. Forester Bernardino Barros Gomes (1839-1910) wrote a book with practical instructions for Cinchona cultivation and chronicled the history of Cinchona plantations in the British and Dutch colonies. In that work he also encouraged private planters to cultivate Cinchona. Forester Adolpho Frederico Möller (1842-1920), as inspector of the Botanical Garden of Coimbra, managed Cinchona plants' cultivation in the garden's nurseries, which were later sent to the colonies, and answered queries from Cinchona planters. Silva's chemistry studies in Germany were crucial to his career and the work of the three scientists was influenced and guided by their knowledge of German science and scientific culture.

Is there association between chronic kidney disease and dental caries? A case-controlled study.

BACKGROUND: The purpose of this study was to assess the association between chronic kidney diseases (CKD) and dental caries. MATERIAL AND METHODS: 107 patients with CKD and 107 with no systemic alteration were randomly included. DMFT (decayed, missing, and filled teeth), plaque index, colony-forming units (CFU) of Streptococcus mutans and salivary composition (IgA total, IgA anti- Streptococcus mutans, calcium and urea) were evaluated. McNemar and Wilcoxon tests were used to compare test and control groups. Spearman test was used to correlate time of hemodialysis and variables studied. Associations between variables were evaluated by logistic regression analysis. RESULTS: The number of filled teeth, the amount of IgA anti-Streptococcus mutans, salivary urea, education level, monthly income and the amount of CFU of Streptococcus mutans were statistically different between groups. There was a positive correlation between the duration of hemodialysis (Hd) and the amount of IgA anti-Streptococcus mutans, urea in saliva, and the number of CFU of Streptococcus mutans. In the adjusted model, a higher incidence of CFU mutans streptococci, elevated salivary urea, smaller number of filled teeth, lower DMFT, and less calcium salivary were associated with CKD. CONCLUSIONS: Programs to prevent and treat oral problems and regular follow-up at the beginning of dialysis are necessary to increase patients' awareness of their condition.

Whole-genome sequencing resolves a polyclonal outbreak by extended-spectrum beta-lactam and carbapenem-resistant Klebsiella pneumoniae in a Portuguese tertiary-care hospital.

Klebsiella pneumoniae has emerged as an important nosocomial pathogen, with whole-genome sequencing (WGS) significantly improving our ability to characterize associated outbreaks. Our study sought to perform a genome-wide analysis of multiclonal K. pneumoniae isolates (n=39; 23 patients) producing extended spectrum beta-lactamases and/or carbapenemases sourced between 2011 and 2016 in a Portuguese tertiary-care hospital. All isolates showed resistance to third-generation cephalosporins and six isolates (five patients) were also carbapenem resistant. Genome-wide-based phylogenetic analysis revealed a topology representing ongoing dissemination of three main sequence-type (ST) clades (ST15, ST147 and ST307) and transmission across different wards, compatible with missing links that can take the form of undetected colonized patients. Two carbapenemase-coding genes were detected: blaKPC-3, located on a Tn4401d transposon, and blaGES-5 on a novel class 3 integron. Additionally, four genes coding for ESBLs (blaBEL-1, blaCTX-M-8, blaCTX-M-15 and blaCTX-M-32) were also detected. ESBL horizontal dissemination across five clades is highlighted by the similar genetic environments of blaCTX-M-15 gene upstream of ISEcp1 on a Tn3-like transposon. Overall, this study provides a high-resolution genome-wide perspective on the epidemiology of ESBL and carbapenemase-producing K. pneumoniae in a healthcare setting while contributing for the adoption of appropriate intervention and prevention strategies.

Antibacterial activity of a novel antimicrobial peptide [W7]KR12-KAEK derived from KR-12 against Streptococcus mutans planktonic cells and biofilms.

The aims of this study were to describe the synthesis of a novel synthetic peptide based on the primary structure of the KR-12 peptide and to evaluate its antimicrobial and anti-biofilm activities against Streptococcus mutans. The antimicrobial effect of KR-12 and [W7]KR12-KAEK was assessed by determining the minimum inhibitory (MIC) and minimum bactericidal (MBC) concentrations. The evaluation of anti-biofilm activity was assessed through total biomass quantification, colony forming unit counting and scanning electron microscopy. [W7]KR12-KAEK showed MIC and MBC values ranging from 31.25 to 7.8 and 62.5 to 15.6 µg ml-1, respectively. Furthermore, [W7]KR12-KAEK significantly reduced biofilm biomass (50-100%). Regarding cell viability, [W7]KR12-KAEK showed reductions in the number of CFUs at concentrations ranging from 62.5 to 7.8 µg ml-1 and 500 to 62.5 µg ml-1 with respect to biofilm formation and preformed biofilms, respectively. SEM micrographs of S. mutans treated with [W7]KR12-KAEK suggested damage to the bacterial surface. [W7]KR12-KAEK is demonstrated to be an antimicrobial agent to control microbial biofilms.

Treatments for intrusive luxation in permanent teeth: a systematic review and meta-analysis.

Intrusive luxation is a severe form of dental trauma and there is no consensus regarding its management for permanent teeth. A systematic review and meta-analysis was performed to identify the appropriate treatment for teeth with intrusive luxation. The PubMed/MEDLINE, Embase, US Clinical Trials, and ISRCTN Registry electronic databases were used to search for articles in English and unpublished studies without a date limit. Eligible studies evaluated periodontal results (root resorption as the primary outcome; marginal bone defects and/or pulpal changes as secondary outcomes) after spontaneous re-eruption (SRE), orthodontic repositioning (ORP), or surgical repositioning (SRP) for patients with one or more traumatically intruded permanent teeth. Risk ratios with 95% confidence intervals were used to compare treatments. The meta-analysis revealed no significant difference (P>0.05) between SRP and SRE for root resorption. For secondary outcomes, SRE was significantly better than SRP and ORP (P<0.05). Subgroup analyses showed no significant differences among treatments in teeth with completely formed roots (P>0.05) and a better prognosis when SRE was performed in teeth with incompletely formed roots (P<0.05). The available evidence does not allow us to conclude on the best treatment for traumatically intruded teeth. More reliable evidence is needed.

Comparative effect of a new mouthrinse containing chlorhexidine, triclosan and zinc on volatile sulphur compounds: a randomized, crossover, double-blind study.

AIM: The aims of this study were to compare the volatile sulphur compounds (VSC)-reducing effect of two commercial mouthrinses using a morning bad breath model and to assess the role of mechanical plaque control (MPC) when performed previously to mouthrinse use. PATIENTS AND METHODS: Eleven volunteers with good oral health were enrolled in a double-blind, randomized, six-step crossover design study with a 7-day washout period. Two commercial mouthrinses were tested using a saline solution (NaCl 0.9%) as a negative control: one mouthrinse contained 0.05% chlorhexidine, 0.05% cetylpyridinium chloride and 0.14% zinc lactate (CHX-CPC-Zn), while the other contained 0.05% chlorhexidine, 0.15% triclosan and 0.18% zinc pidolate (CHX-triclosan-Zn). A portable sulphide monitor (Halimeter(®) ) was used for VSC quantification. Measurements were made at baseline, and 1, 3 and 5 h after rinsing. Significant differences were detected by analysis of variance. RESULTS: No significant differences between groups were detected at baseline. We were unable to demonstrate a significant influence of mechanical plaque control on the reduction of VSC levels when performed before mouthrinse use (P = 0.631). Both mouthrinses effectively lowered VSC levels in all test intervals (P < 0.05). No statistically significant differences were found between mouthrinses in any of the test intervals (P = 0.629, 0.069 and 0.598 at 1, 3 and 5 h). CONCLUSION: This study demonstrated that CHX-CPC-Zn and CHX-triclosan-Zn have significant and similar effects in reducing VSC levels, which persist for at least 5 h. Such effects were independent of previous MPC, which failed to improve on the results of mouthrinse use alone.

Effects of the naturally-occurring contaminant microcystins on the Azolla filiculoides-Anabaena azollae symbiosis.

Harmful algal blooms (HABs) contaminate aquatic ecosystems and are responsible for animal poisoning worldwide. We conducted a toxicity test with the aquatic fern and the biofertilizer, Azolla filiculoides. The sporophytes were exposed to three concentrations (0.01, 0.1 and 1µgmL(-1)) of a microcystin (MC) cyanobacterial crude extract and purified MC-LR. The growth of A. filiculoides decreased only at 1µgmL(-1) crude extract concentration while with MC-LR it decreased at all the tested concentrations, indicating that the presence of other compounds in the crude extract altered toxicity and stimulated the fern growth at lower concentrations (0.01 and 0.1µgmL(-1)). Both phycoerythrocyanin and allophycocyanin levels decreased in all the concentrations of crude extract and MC-LR. The phycocyanin had a marked increase at 0.1µgmL(-1) crude extract concentration and a marked decrease at 1µgmL(-1) MC-LR concentration. These changes in the phycobiliprotein content indicate a shift in the antenna pigments of the cyanobionts of A. filiculoides. The changes in two oxidative stress enzymes, glutathione reductase for the crude extract assay and glutathione peroxidase for MC-LR assay, points towards the induction of stress defense responses. The low bioconcentration factor in both crude extract and MC-LR treatments can suggest the low uptake of microcystins, and indicates that the aquatic fern can be used as a biofertilizer and as animal feed but is not suitable for MC phytoremediation.

Central mediators involved in the febrile response induced by polyinosinic-polycytidylic acid: lack of involvement of endothelins and substance P.

The present study evaluated the involvement of interleukin(IL)-1ß, tumor necrosis factor-α (TNF-α), IL-6, interferon(IFN)-γ, prostaglandins of the E2 series, endothelins, substance P and opioids within the central nervous system in polyinosinic:polycytidylic acid (Poly I:C)-induced fever in rats. Poly I:C injection induced a febrile response which was reduced by intracerebroventricular administration of the antibodies against TNF-α, IL-6, or IFN-γ, or by IL-1 or µ receptor antagonists. Intraperitoneal injection of indomethacin or oral administration of celecoxib also reduced Poly I:C-induced fever. Poly I:C increased prostaglandin E2 levels in the cerebrospinal fluid of the animals which was also reduced by indomethacin. The intracerebroventricular injection of ETB or NK1 receptor antagonists did not alter Poly I:C-induced fever. These data suggest the involvement of IL-1ß, TNF-α, IL-6, IFN-γ, prostaglandin E2, and opioids but not endothelins and substance P on Poly I:C-induced fever.

Pressure effects on the vibrational properties of α-Bi(2)O(3): an experimental and theoretical study.

We report an experimental and theoretical high-pressure study of the vibrational properties of synthetic monoclinic bismuth oxide (α-Bi(2)O(3): ), also known as mineral bismite. The comparison of Raman scattering measurements and theoretical lattice-dynamics ab initio calculations is key to understanding the complex vibrational properties of bismite. On one hand, calculations help in the symmetry assignment of phonons and to discover the phonon interactions taking place in this low-symmetry compound, which shows considerable phonon anticrossings; and, on the other hand, measurements help to validate the accuracy of first-principles calculations relating to this compound. We have also studied the pressure-induced amorphization (PIA) of synthetic bismite occurring around 20 GPa and showed that it is reversible below 25 GPa. Furthermore, a partial temperature-induced recrystallization (TIR) of the amorphous sample can be observed above 20 GPa upon heating to 200°C, thus evidencing that PIA at room temperature occurs because of the inability of the α phase to undergo a phase transition to a high-pressure phase. Raman scattering measurements of the TIR sample at room temperature during pressure release have been performed. The interpretation of these results in the light of ab initio calculations of the candidate phases at high pressures has allowed us to tentatively attribute the TIR phase to the recently found high-pressure hexagonal HPC phase and to discuss its lattice dynamics.

Etanercept reduces thermal and mechanical orofacial hyperalgesia following inflammation and neuropathic injury.

BACKGROUND: This study evaluated the involvement of tumour necrosis factor α (TNF-α) in orofacial thermal and mechanical hyperalgesia induced by an inflammatory stimulus or by chronic constriction of the infraorbital nerve (CION) using etanercept (Eta), a TNF-receptor fusion protein that inhibits TNF-α action. METHODS: Animals were treated with Eta (0.5 and 5.0 mg/kg, s.c.) or dexamethasone (Dex, 0.5, 1.0 and 2.0 mg/kg, s.c.) and orofacial thermal (cold and heat) and mechanical hyperalgesia induced by an inflammatory stimulus (carrageenan, Cg 50 and 100 µg/lip) or by chronic CION, a model of neuropathic pain in the orofacial region was evaluated. Treatments with Dex or Eta were carried out before Cg or before or after CION. RESULTS: Eta or Dex abolished inflammatory thermal and mechanical hyperalgesia. Also, each drug, when given at the day of the surgery and the subsequent day, was effective to abolish thermal and mechanical hyperalgesia induced by CION, assessed on day 4 and on day 13 after the surgery, respectively. However, Eta, but not Dex, given after the CION, abolished thermal and mechanical hyperalgesia and reduced TNF-α level in the trigeminal ganglion. CONCLUSIONS: These results suggest that TNF-α has an important role in cold, heat and mechanical hyperalgesia induced by inflammation or neuropathy in the orofacial region and this may contribute for the establishment of new therapeutic strategies to treat orofacial pain.

Structural study of α-Bi2O3 under pressure.

An experimental and theoretical study of the structural properties of monoclinic bismuth oxide (α-Bi2O3) under high pressures is here reported. Both synthetic and mineral bismite powder samples have been compressed up to 45 GPa and their equations of state have been determined with angle-dispersive x-ray diffraction measurements. Experimental results have been also compared with theoretical calculations which suggest the possibility of several phase transitions below 10 GPa. However, experiments reveal only a pressure-induced amorphization between 15 and 25 GPa, depending on sample quality and deviatoric stresses. The amorphous phase has been followed up to 45 GPa and its nature discussed.

Use of phages against antibiotic-resistant Staphylococcus aureus isolated from bovine mastitis.

Bovine mastitis is the primary disease of dairy cattle worldwide and it causes large economic losses. Among several microorganisms that are the causative agents of this disease, Staphylococcus aureus is the most prevalent. Although antibiotic therapy is still the most widely used procedure for the treatment of bovine mastitis, alternative means of treatment are necessary due to the presence of antibiotic residues in milk, which is a growing concern because of its interference with the production of milk derivatives and the selection of resistant bacterial strains. The use of bacteriophages as a tool for the control of pathogens is an alternative treatment to antibiotic therapy. In this work, to obtain phages with the potential for use in phage therapy as a treatment for mastitis, we isolated and identified the bacteria from the milk of mastitis-positive cows. A total of 19% of the animals from small and medium farms of the Zona da Mata Mineira, Brazil, was positive for bovine mastitis, and bacteria of the genus Staphylococcus were the most prevalent pathogens. The majority of the S. aureus isolates tested was resistant to penicillin and ampicillin. In parallel, we isolated 10 bacteriophages able to infect some of these S. aureus isolates. We determined that these phages contained DNA genomes of approximately 175 kb in length, and the protein profiles indicated the presence of 4 major proteins. Electron microscopy revealed that the phages are caudate and belong to the Myoviridae family. The isolates exhibited interesting features for their use in phage therapy such as a high lytic potential, a wide range of hosts, and thermostability, all of which favor their use in the field.

Electroretinography in dogs using a fiber electrode prototype.

We compared two electroretinography (ERG) electrodes in dogs using ERG standards of the International Society for Clinical Electrophysiology of Vision (ISCEV). Ten healthy Yorkshire terrier dogs (mean age, 2.80 ± 1.42 years; 6 females) weighing 5.20 ± 1.56 kg were evaluated using an ERG system for veterinary use. Dark- and light-adapted ERG responses were recorded using an ERG-Jet electrode and a fiber electrode prototype. The examinations were performed during 2 visits, 3 weeks apart. Both electrodes (ERG-Jet or fiber prototype) were used on each animal and the first eye to be recorded (OD × OS) was selected randomly. Three weeks later the examination was repeated on the same animal switching the type of electrode to be used that day and the first eye to be examined. The magnitude and waveform quality obtained with the two electrode types were similar for all ERG responses. ERG amplitudes and implicit times obtained from dogs using the fiber electrode prototype were comparable to those obtained with the ERG-Jet electrode for rod, maximal rod-cone summed, cone, and 30-Hz flicker responses. The fiber electrode prototype is a low-cost device, available as an alternative instrument for clinical veterinary ERG recording for retinal function assessment.

Electroretinography in dogs using a fiber electrode prototype

We compared two electroretinography (ERG) electrodes in dogs using ERG standards of the International Society for Clinical Electrophysiology of Vision (ISCEV). Ten healthy Yorkshire terrier dogs (mean age, 2.80 ± 1.42 years; 6 females) weighing 5.20 ± 1.56 kg were evaluated using an ERG system for veterinary use. Dark- and light-adapted ERG responses were recorded using an ERG-Jet electrode and a fiber electrode prototype. The examinations were performed during 2 visits, 3 weeks apart. Both electrodes (ERG-Jet or fiber prototype) were used on each animal and the first eye to be recorded (OD × OS) was selected randomly. Three weeks later the examination was repeated on the same animal switching the type of electrode to be used that day and the first eye to be examined. The magnitude and waveform quality obtained with the two electrode types were similar for all ERG responses. ERG amplitudes and implicit times obtained from dogs using the fiber electrode prototype were comparable to those obtained with the ERG-Jet electrode for rod, maximal rod-cone summed, cone, and 30-Hz flicker responses. The fiber electrode prototype is a low-cost device, available as an alternative instrument for clinical veterinary ERG recording for retinal function assessment.

Occurrence of furan in commercial processed foods in Brazil.

Selected commercial processed foods available in the Brazilian market (306 samples) were analysed for furan content using a validated gas chromatography-mass spectrometry method preceded by headspace solid phase micro-extraction (HS-SPME-GC/MS). Canned and jarred foods, including vegetable, meat, fruit and sweet products, showed levels up to 32.8 µg kg⁻¹, with the highest concentrations observed in vegetables and meats. For coffee, furan content ranged from 253.0 to 5021.4 µg kg⁻¹ in the roasted ground coffee and from not detected to 156.6 µg kg⁻¹ in the beverage. For sauces, levels up to 138.1 µg kg⁻¹ were found. In cereal-based products, the highest concentrations (up to 191.3 µg kg⁻¹) were observed in breakfast cereal (corn flakes), cracker (cream crackers) and biscuit (wafer). In general, these results are comparable with those reported in other countries and will be useful for a preliminary estimate of the furan dietary intake in Brazil.

Preliminary results on the effects of grape (Vitis vinifera) seed condensed tannins on in vitro intestinal digestibility of the lupin (Lupinus angustifolius) seed protein fraction in small ruminants.

Condensed tannins (CT) from grape seeds (Vitis vinifera L.) were added to complex the protein fraction of Lupinus angustifolius seeds. Three CT/protein ratios were used: 96 mg/g (T(1)), 180 mg/g (T(2)) and 0 mg/g (T(0)). The CP losses in the rumen were assessed by the nylon-bag technique and CP intestinal digestibility (CPID) was estimated using an in vitro assay applying a three-step procedure: samples were subject to rumen degradation (in situ, 16 h) and the remaining residues were subject to the digestive enzymes of the abomasum and pancreas in vitro. A positive effect (p < 0.05) of the level of CT on the immediately soluble faction a and the insoluble degradable fraction b was observed between T(0) and T(2) . In the presence of CT the rumen degradation rate was reduced (p < 0.05) from 0.0763/h (T(0)) to 0.0443/h (T(2)). The application of CT showed a reduction (around 10% for T(1)) of effective rumen CP degradability. The CPID did not seem to be affected (p > 0.05) by the presence of CT. These findings suggest that the use of grape seed CT might have the potential to improve the efficiency of utilisation of the protein fraction from lupin seeds.

Azolla-Anabaena's behaviour in urban wastewater and artificial media--influence of combined nitrogen.

The results of using the nitrogen fixing symbiotic system Azolla-Anabaena to improve the quality of treated urban wastewater, particularly on what concerns phosphorus removal efficiencies (40-65%), obtained in continuous assays performed during the past few years and presented earlier, were very promising. Nevertheless, the presence of combined nitrogen in some wastewaters can compromise the treatment efficiency. The main goal of this work was to compare plants behaviour in wastewater and in mineral media with and without added nitrogen. Azolla filiculoides's specific growth rates in wastewater and in mineral media without added nitrogen or with low nitrate concentration were very similar (0.122 d(-1)-0.126 d(-1)), but decreased in the presence of ammonium (0.100 d(-1)). The orthophosphate removal rate coefficients were similar in all the growth media (0.210 d(-1)-0.232 d(-1)), but ammonium removal rate coefficient in wastewater was higher (0.117 d(-1)) than in mineral medium using that source of nitrogen (0.077 d(-1)). The ammonium present in wastewater, despite its high concentration (34 mg NL(-1)), didn't seem to inhibit growth and nitrogen fixation, however, in mineral media, ammonium (40 mg NL(-1)) was found to induce, respectively, 18% and 46% of inhibition.

The use of visible and near infrared reflectance spectroscopy to predict beef M. longissimus thoracis et lumborum quality attributes.

Visible and near infrared reflectance spectroscopy was used to predict pH at 24h (pH24) post-mortem, sarcomere length (SL), cooking loss (CL), Warner-Bratzler Shear Force (WBSF) and colour parameters (L(∗), a(∗), b(∗)) in beef cattle samples. Samples from M. longissimus thoracis et lumborum from 30 bulls were aged at 4°C for 1, 3, 7 and 14 days and analysed for pH, SL, CL, WBSF and colour. NIRS calibrations for pH24, luminosity at 0 (L(∗)t0) and 60min (L(∗)t60) showed good predictability (R(2)=0.97, 0.85 and 0.82; SECV=0.10, 1.16, 1.36, respectively), whereas those related to the rest of the parameters were poorer.