Research progress on biodegradable polymeric platforms for targeting antibiotics to the bone.

The treatment of bone infections still involves systemic or local antibiotic therapy in high doses for prolonged periods. Current research focuses on the application of different drug delivery systems to the bone, aiming at a targeted local administration that will decrease the number of drugs used and their toxicity, compared to the systemic route. The gold standard in clinical practice is currently poly(methyl methacrylate) (PMMA) cement. The main drawback of PMMA, however, is that it is non-biodegradable, requiring a second follow-up surgery to remove the implant. Biodegradable delivery systems, on the other hand, are easily resorbable within the organism, and less invasive alternative with better patient compliance. Among biodegradable materials, natural and synthetic polymers are being studied as local drug delivery systems due to their excellent biocompatibility, sustained effect, and antibiotic release with high penetrability to infected bone and soft tissue. In this review, we focus on biodegradable polymeric platforms, such as micro- and nanoparticles, scaffolds, and hydrogels, as well as multi-delivery systems for targeting antibiotics to the bone. Additionally, we discuss the reported drug release profiles that provide important information about the systems' functionality.

Poly(DL-lactic acid) scaffolds as a bone targeting platform for the co-delivery of antimicrobial agents against S. aureus-C.albicans mixed biofilms.

New strategies for the treatment of polymicrobial bone infections are required. In this study, the co-delivery of two antimicrobials by poly(D,L-lactic acid) (PDLLA) scaffolds was investigated in a polymicrobial biofilm model. PDLLA scaffolds were prepared by solvent casting/particulate leaching methodology, incorporating minocycline and voriconazole as clinically relevant antimicrobial agents. The scaffolds presented a sponge-like appearance, suitable to support cell proliferation and drug release. Single- and dual-species biofilm models of Staphylococcus aureus and Candida albicans were developed and characterized. S. aureus presented a higher ability to form single-species biofilms, compared to C. albicans. Minocycline and voriconazole-loaded PDLLA scaffolds showed activity against S. aureus and C. albicans single- and dual-biofilms. Ultimately, the cytocompatibility/functional activity of PDLLA scaffolds observed in human MG-63 osteosarcoma cells unveil their potential as a next-generation co-delivery system for antimicrobial therapy in bone infections.

Adenosine A2A receptor regulation of microglia morphological remodeling-gender bias in physiology and in a model of chronic anxiety.

Developmental risk factors, such as the exposure to stress or high levels of glucocorticoids (GCs), may contribute to the pathogenesis of anxiety disorders. The immunomodulatory role of GCs and the immunological fingerprint found in animals prenatally exposed to GCs point towards an interplay between the immune and the nervous systems in the etiology of these disorders. Microglia are immune cells of the brain, responsive to GCs and morphologically altered in stress-related disorders. These cells are regulated by adenosine A2A receptors, which are also involved in the pathophysiology of anxiety. We now compare animal behavior and microglia morphology in males and females prenatally exposed to the GC dexamethasone. We report that prenatal exposure to dexamethasone is associated with a gender-specific remodeling of microglial cell processes in the prefrontal cortex: males show a hyper-ramification and increased length whereas females exhibit a decrease in the number and in the length of microglia processes. Microglial cells re-organization responded in a gender-specific manner to the chronic treatment with a selective adenosine A2A receptor antagonist, which was able to ameliorate microglial processes alterations and anxiety behavior in males, but not in females.

Use of 3,3',5,5' tetramethylbenzidine as new electrochemical indicator of DNA hybridization and its application in genossensor.

Electrochemical tools are important biosensor platforms for disease diagnosis, due to their speediness, easiness, low cost and portability. However, for DNA detection, the use of indicators and/or intercalators is necessary to improve electrochemical sensitivity. Currently, ethidium bromide (EthBr) is the cheapest and most used DNA intercalators, but presents carcinogenic and teratogenic properties. Other indicators may be important for DNA photonic detection, and besides being more expensive, they behave similarly to EthBr. This investigation shows for the first time the use of tetramethylbenzidine(TMB) as a new remarkable non-carcinogenic DNA indicator for genosensing purposes, which may be used for nucleic acid detection of microorganisms, based on complementarity of base-pairing between probe and target molecules. The results indicate that TMB can be used as a new electrochemical indicator readily applicable in genosensors, which is able to detect the hybridization of single stranded DNA probe with its complementary target strand. An additional advantage of TMB, beside its non-genotoxicity, is the electrochemical reduction property, which prevents interference of serum components and other oxidative samples in the electrochemical analysis.

Functional hypothalamic amenorrhoea: leptin treatment, dietary intervention and counselling as alternatives to traditional practice - systematic review.

Functional hypothalamic amenorrhoea (FHA) is a neuroendocrine disorder caused by an energy deficit and characterized by low leptin levels. Based on this, previous studies have suggested that leptin administration may play a crucial role in FHA treatment. However, FHA is also associated with abnormal psychosocial and dietary behaviour that needs to be addressed. In this context, this systematic review examined the efficacy of leptin treatment, non-pharmacological therapy and nutritional interventions in FHA. PubMed, Medline and Cochrane Library databases were searched in order to find relevant papers, including randomized controlled trials, clinical trials, prospective studies and case reports. The effects of different treatments on reproductive function, hormonal status and bone markers were recorded. Studies regarding other forms of treatment were excluded. In total, 111 papers were retrieved. After the removal of 29 duplicate papers, the abstracts and titles of 82 papers were examined. Subsequently, 53 papers were excluded based on title, and seven papers were omitted based on abstract. The remaining 11 papers were used: three based on leptin treatment, three regarding non-pharmacological treatment and five regarding dietary intervention. This literature review indicates that all of these treatment strategies improved reproductive function and hormonal status significantly, although conclusive results could not be drawn on bone markers. While leptin may be a promising new treatment, social aspects of FHA should also be addressed. As a result, a multifaceted therapeutic approach should be applied to treat affected women.

Occurrence of natural triploidy in Rhamdia quelen (Siluriformes, Heptapteridae).

Five specimens of Rhamdia quelen collected from the Lindóia Stream, PR, Brazil, were cytogenetically analyzed. The diploid chromosome number found was 58, including 30 metacentric, 16 submetacentric, 10 subtelocentric, and 2 acrocentric chromosomes. Supernumerary or B chromosomes, frequently observed in this fish group, were not detected. One of the individuals was triploid, with 3n = 87. A silver-stained nucleolar organizer region was found on a pair of submetacentric chromosomes of the diploid specimens, and on three chromosomes of the triploid individual, confirming triploidy. Treatment with fluorochrome chromomycin A(3) revealed fluorescent bands coincident with those of the silver-stained nucleolar organizer region, in both diploid and triploid individuals, showing that this is a GC-rich region. Heterochromatin distribution was visualized by the C-banding technique, mainly in the terminal chromosome regions of the individuals and was also observed in the pericentromeric regions of some chromosomes and at both telomeres.

Cytogenetic analysis of the 18S, 5S rDNA and B chromosome of Iheringichthys labrosus (Lütken, 1874) (Siluriformes, Pimelodidae) / Análise Citogenética de DNAr 18S, 5S e cromossomo B de Iheringichthys labrosus (Lütken, 1874) (Siluriformes, Pimelodidae)

Cytogenetic analyses of the location of 18S and 5S ribosomal DNAs, and the base composition of B chromosomes of Iheringichthys labrosus from Tibagi River, Paraná, Brazil, are provided. AgNORs were observed in the terminal position on the long arm of a subtelocentric chromosome pair. CMA3-positive staining was observed in some chromosomes, which besides being associated with NORs, were all DAPI-negative. Chromosome B showed a strong fluorescence with CMA3. The concomitant use of 18S and 5S rDNA probes using the FISH technique revealed 18S ribosomal cistrons in a pair of subtelocentric chromosomes, on the long arm in the terminal position, coinciding with the AgNOR. The 5S sites were found in another subtelocentric pair, on the long arm in the interstitial region, near the centromere. The findings of the present study suggest that, although there are some more conserved cytogenetic characteristics, populations of I. labrosus may show their own characteristics.

Foram realizadas análises citogenéticas em Iheringichthys labrosus do Rio Tibagi, Paraná, Brasil com a localização cromossômica dos DNAs ribossômicos 18S e 5S e a composição de bases de seus cromossomos B. As AgNORs foram observadas em posição terminal, no braço longo de um par de cromossomos subtelocêntricos. Marcações CMA3 positivas foram observadas em alguns cromossomos e associadas com as RONs. Porém, todas estas marcações apresentaram-se DAPI negativas. O cromossomo B mostrou-se fortemente fluorescente com CMA3. O uso concomitante das sondas de DNAr 18S e 5S, através da técnica de FISH, revelou os cístrons ribossômicos em um par de cromossomos subtelocêntricos, em posição terminal do braço longo, coincidindo com a AgNOR. Os sítios 5S foram observados em outro par subtelocêntrico, em posição intersticial do braço longo, próximo ao centrômero. Os resultados observados no presente estudo sugerem que, embora existam algumas características citogenéticas mais conservadas, as populações de I. labrosus podem mostrar suas próprias características.

Occurrence of B chromosomes in Cyphocharax modestus (Fernández-Yépez, 1948) and Steindachnerina insculpta (Fernández-Yépez, 1948)(Characiformes, Curimatidae) from the Tibagi River basin (Paraná State, Brazil)

We cytogenetically analyzed 18 individuals of Cyphocharax modestus, and 41 individuals of Steindachnerina insculpta from the Tibagi River basin (Paraná State, Brazil). All the specimens had 2n = 54 chromosomes, all meta-submetacentric (M-SM). The presence of 1 or 2 B chromosomes was seen in some individuals of C. modestus of the two sampled populations, showing inter- and intra individual variation. In S. insculpta, B chromosomes were also observed but only in one population, also showing inter- and intra individual variation. C-banding was used to show that the identified B chromosomes were totally heterochromatic in the two examined species.

Foram analisados, citogeneticamente, 18 indivíduos de Cyphocharax modestus e 41 indivíduos de Steindachnerina insculpta da bacia do rio Tibagi (Paraná, Brasil). Todos os espécimes apresentaram 2n = 54 cromossomos, todos do tipo meta-submetacêntrico (M-SM). A presença de 1 ou 2 cromossomos B foi detectada em alguns indivíduos de C. modestus de duas populações amostradas, evidenciando uma variação inter e intraindividual. Em S. insculpta, também foram observados cromossomos B, embora em somente uma população, mostrando também uma variação inter e intraindividual. Bandamento C foi usado para mostrar que os cromossomos B identificados apresentaram-se totalmente heterocromáticos nas duas espécies examinadas.

Occurrence of B chromosomes in Cyphocharax modestus (Fernández-Yépez, 1948) and Steindachnerina insculpta (Fernández-Yépez, 1948)(Characiformes, Curimatidae) from the Tibagi River basin (Paraná State, Brazil)

We cytogenetically analyzed 18 individuals of Cyphocharax modestus, and 41 individuals of Steindachnerina insculpta from the Tibagi River basin (Paraná State, Brazil). All the specimens had 2n = 54 chromosomes, all meta-submetacentric (M-SM). The presence of 1 or 2 B chromosomes was seen in some individuals of C. modestus of the two sampled populations, showing inter- and intra individual variation. In S. insculpta, B chromosomes were also observed but only in one population, also showing inter- and intra individual variation. C-banding was used to show that the identified B chromosomes were totally heterochromatic in the two examined species.

Foram analisados, citogeneticamente, 18 indivíduos de Cyphocharax modestus e 41 indivíduos de Steindachnerina insculpta da bacia do rio Tibagi (Paraná, Brasil). Todos os espécimes apresentaram 2n = 54 cromossomos, todos do tipo meta-submetacêntrico (M-SM). A presença de 1 ou 2 cromossomos B foi detectada em alguns indivíduos de C. modestus de duas populações amostradas, evidenciando uma variação inter e intraindividual. Em S. insculpta, também foram observados cromossomos B, embora em somente uma população, mostrando também uma variação inter e intraindividual. Bandamento C foi usado para mostrar que os cromossomos B identificados apresentaram-se totalmente heterocromáticos nas duas espécies examinadas.

Morphological, agronomical and pharmacological characterization of Hyptis pectinata (L.) Poit germplasm

Several species of the genus Hyptis have presented medicinal characteristics and are frequently indicated to treat gastro intestinal infections, gramps and pain, as well as for skin infections. Three harvests were carried out using six H. pectinata accessions, and the following characteristics were evaluated: plant height, canopy diameter, leave length (L) and width (W), L/W relation and dry weight of leaves and stem. The accession SAM006 have presented highest leave dry matter yield when the three harvests were summed. The aqueous leaf extracts of the same six H. pectinata accessions were tested for anti-edematogenic effect using the carrageenin-induced rat paw edema at doses of 200, 400 and 600 mg/kg. The extracts administered orally had a significant anti-edematogenic effect. The dose of 200 mg/kg of accessions SAM004 and SAM005 had a stronger effect reducing the edema by 19.6 percent and 15.4 percent, respectively. Similar results were obtained using higher dosages of the aqueous extract of the accessions SAM002, SAM003 and SAM006. It can be concluded that the accessions SAM004, SAM005 and SAM006 are promising genotypes for a plant breeding program that aims the development of a cultivar with highest leave yielding and anti-edematogenic effect.