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1.
Viruses ; 15(12)2023 12 15.
Article in English | MEDLINE | ID: mdl-38140675

ABSTRACT

The COVID-19 pandemic caused by the SARS-CoV-2 (ß-CoV) betacoronavirus has posed a significant threat to global health. Despite the availability of vaccines, the virus continues to spread, and there is a need for alternative strategies to alleviate its impact. Vitamin D, a secosteroid hormone best known for its role in bone health, exhibits immunomodulatory effects in certain viral infections. Here, we have shown that bioactive vitamin D (calcitriol) limits in vitro replication of SARS-CoV-2 and murine coronaviruses MHV-3 and MHV-A59. Comparative studies involving wild-type mice intranasally infected with MHV-3, a model for studying ß-CoV respiratory infections, confirmed the protective effect of vitamin D in vivo. Accordingly, mice fed a standard diet rapidly succumbed to MHV-3 infection, whereas those on a vitamin D-rich diet (10,000 IU of Vitamin D3/kg) displayed increased resistance to acute respiratory damage and systemic complications. Consistent with these findings, the vitamin D-supplemented group exhibited lower viral titers in their lungs and reduced levels of TNF, IL-6, IL-1ß, and IFN-γ, alongside an enhanced type I interferon response. Altogether, our findings suggest vitamin D supplementation ameliorates ß-CoV-triggered respiratory illness and systemic complications in mice, likely via modulation of the host's immune response to the virus.


Subject(s)
Murine hepatitis virus , Pneumonia , Mice , Humans , Animals , Vitamin D , Pandemics/prevention & control , Murine hepatitis virus/physiology , SARS-CoV-2 , Vitamins/pharmacology , Vitamins/therapeutic use , Diet
2.
Tissue Cell ; 80: 101988, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36521234

ABSTRACT

Bacillus Calmette-Guérin (BCG)-based intravesical immunotherapy has been applied as gold standard treatment for high-risk non-muscle invasive bladder cancer (NMIBC) for almost half a century. However, several patients with high-risk disease experience relapse, including those whose condition has worsened and who failed to respond to BCG. Non-significant therapeutic options have been developed for these at-risk patients, for many years. Immunotherapies have shown promising outcomes for bladder cancer treatment. Accordingly, our research group developed the OncoTherad® (MRB-CFI-1) immunotherapy, which has shown positive outcomes in NMIBC treatment. The aim of the current study is to describe, in details, the physicochemical features and potential action mechanisms of OncoTherad® nano-immunotherapy, based on toll-like receptor 4 (TLR4)-mediated interferon and on RANK/RANKL signaling pathways, in animal model with NMIBC. Based on the current findings, OncoTherad® nano-immunotherapy did not have genotoxic effect on the investigated model and did not show signs of limiting local and/or systemic toxicity at therapeutic doses. OncoTherad® nano-immunotherapy was more effective than the BCG treatment, since it reduced by 70% the malignancy rate. Furthermore, it was possible identifying an important action mechanism of OncoTherad®, which was based on the modulation of TLR4-mediated interferon and RANK/RANKL signaling pathways that, altogether, were essential to reduce malignancy rate. OncoTherad® mechanisms in these pathways helped preventing tumor recurrence.


Subject(s)
Non-Muscle Invasive Bladder Neoplasms , Urinary Bladder Neoplasms , Animals , Toll-Like Receptor 4 , BCG Vaccine/therapeutic use , Urinary Bladder Neoplasms/drug therapy , Urinary Bladder Neoplasms/pathology , Immunotherapy , Interferons/therapeutic use
3.
Int J Oral Maxillofac Surg ; 52(1): 51-59, 2023 Jan.
Article in English | MEDLINE | ID: mdl-35934567

ABSTRACT

The aim of this systematic review and meta-analysis was to assess whether the presence of inferior third molars during sagittal split mandibular ramus osteotomy increases the risk of intraoperative and postoperative complications. The PRISMA protocol was followed in this study, and the review was registered in the PROSPERO database (CRD42020147642). A search was conducted in the MEDLINE (PubMed), Web of Science, Cochrane Central, and Scopus databases on November 1, 2021. Nineteen articles were included, and the variables analysed were unfavourable fractures, infection, neurosensory disturbance, removal of osteosynthesis material, and duration of surgery. Meta-analyses were performed for the variables unfavourable fractures (risk ratio (RR) 0.95, 95% confidence interval (CI) 0.58-1.57, P = 0.84), infection (RR 0.75, 95% CI 0.48-1.18, P = 0.21), and neurosensory disturbance (RR 1.55, 95% CI 0.61-3.91, P = 0.35); no statistically significant difference in the risk of these variables was found between the groups with and without third molars. The third molars did not increase the need to remove fixation material, but increased the surgery time. The presence of the third molar during sagittal split mandibular ramus osteotomy appears not to increase the risk of intraoperative and postoperative complications. The results presented here must be interpreted with caution due to the heterogeneity presented by the observational studies included.


Subject(s)
Molar, Third , Osteotomy, Sagittal Split Ramus , Humans , Osteotomy, Sagittal Split Ramus/adverse effects , Osteotomy, Sagittal Split Ramus/methods , Molar, Third/surgery , Mandible/surgery , Postoperative Complications/epidemiology , Operative Time
4.
Tissue Cell ; 76: 101762, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35245856

ABSTRACT

The new modalities for treating patients with high-grade non-muscle invasive bladder cancer (HGNMIBC) for whom Bacillus Calmette-Guerin (BCG) has failed or is contraindicated are recently increasing due to the development of new drugs. Since NMIBC is sensitive to immunotherapy, Toll-like receptors (TLRs) agonist compounds may represent a potential antitumor therapeutic approach. Our research group developed a synthetic compound, with antitumor and immunological properties, called OncoTherad® (MRB-CFI-1). To evaluate the effects of OncoTherad® (MRB-CFI-1) and its compounds (P14-16 and CFI-1), thirty-six female C57Bl/6 J mice were divided into six groups (n = 6): Control, Cancer, Cancer + BCG (40 mg), Cancer + OncoTherad® (20 mg/mL), Cancer + P14-16 (20 mg/mL) and Cancer + CFI-1 (20 mg/mL). NMIBC was chemically induced (N-ethyl-N-nitrosourea 50 mg/mL) and the treatments were followed for six weeks. The bladder was collected and routinely processed for immunohistochemical analyses of the Toll-Like receptors signaling pathway (TLR2, TLR4, MyD88, IRF-3, IKK-α, NF-kB, TNF-α, TRIF, IFN-γ, IL-6). The results obtained showed that the tumor progression was 100 % reduced on OncoTherad® (MRB-CFI-1) treated animals. Immunohistochemical analysis demonstrated that while the conventional BCG treatment stimulated the canonic pathway, OncoTherad® (MRB-CFI-1) stimulated the non-canonical pathway (increasing expression of TLR4, TRIF, IRF, and IFNγ). OncoTherad® (MRB-CFI-1) could be considered a promising therapy in the treatment of NMIBC.


Subject(s)
Glycoproteins , Mycobacterium bovis , Nanostructures , Phosphates , Toll-Like Receptors , Urinary Bladder Neoplasms , Animals , BCG Vaccine/pharmacology , Female , Glycoproteins/pharmacology , Humans , Immunotherapy/methods , Mice , Nanostructures/administration & dosage , Signal Transduction/drug effects , Toll-Like Receptors/metabolism , Urinary Bladder Neoplasms/drug therapy , Urinary Bladder Neoplasms/pathology
5.
Osteoporos Int ; 31(7): 1341-1352, 2020 Jul.
Article in English | MEDLINE | ID: mdl-32123938

ABSTRACT

We have sought the molecular diagnosis of OI in 38 Brazilian cases through targeted sequencing of 15 candidate genes. While 71% had type 1 collagen-related OI, defects in FKBP10, PLOD2 and SERPINF1, and a potential digenic P3H1/WNT1 interaction were prominent causes of OI in this underrepresented population. INTRODUCTION: Defects in type 1 collagen reportedly account for 85-90% of osteogenesis imperfecta (OI) cases, but most available molecular data has derived from Sanger sequencing-based approaches in developed countries. Massively parallel sequencing (MPS) allows for systematic and comprehensive analysis of OI genes simultaneously. Our objective was to obtain the molecular diagnosis of OI in a single Brazilian tertiary center cohort. METHODS: Forty-nine individuals (84% adults) with a clinical diagnosis of OI, corresponding to 30 sporadic and 8 familial cases, were studied. Sixty-three percent had moderate to severe OI, and consanguinity was common (26%). Coding regions and 25-bp boundaries of 15 OI genes (COL1A1, COL1A2, IFITM5 [plus 5'UTR], SERPINF1, CRTAP, P3H1, PPIB, SERPINH1, FKBP10, PLOD2, BMP1, SP7, TMEM38B, WNT1, CREB3L1) were analyzed by targeted MPS and variants of interest were confirmed by Sanger sequencing or SNP array. RESULTS: A molecular diagnosis was obtained in 97% of cases. COL1A1/COL1A2 variants were identified in 71%, whereas 26% had variants in other genes, predominantly FKBP10, PLOD2, and SERPINF1. A potential digenic interaction involving P3H1 and WNT1 was identified in one case. Phenotypic variability with collagen defects could not be explained by evident modifying variants. Four consanguineous cases were associated to heterozygous COL1A1/COL1A2 variants, and two nonconsanguineous cases had compound PLOD2 heterozygosity. CONCLUSIONS: Novel disease-causing variants were identified in 29%, and a higher proportion of non-collagen defects was seen. Obtaining a precise diagnosis of OI in underrepresented populations allows expanding our understanding of its molecular landscape, potentially leading to improved personalized care in the future.


Subject(s)
Osteogenesis Imperfecta , Adult , Brazil , Collagen Type I/genetics , Heterozygote , Humans , Mutation , Osteogenesis Imperfecta/genetics , Tacrolimus Binding Proteins/genetics
6.
Osteoporos Int ; 31(5): 905-912, 2020 May.
Article in English | MEDLINE | ID: mdl-31897546

ABSTRACT

The congenital adrenal hyperplasia population seems to have an intrinsic tendency to a high frequency of low bone mass. However in this single-center and long-term evaluated cohort, the simplified corticoid regimen, with exclusive dexamethasone single dose reposition during adulthood, did not represent a risk factor for decrease in bone health. INTRODUCTION: The impact of long-term and supposedly physiological doses of gluco and mineralocorticoid (GC/MC) on bone mineral density (BMD) in congenital adrenal hyperplasia (CAH) remains discordant among studies, which contain different clinical forms and corticoid regimens. Our aim was to evaluate the BMD in CAH adults receiving similar GC regimen since childhood and to correlate it with GC/MC cumulative doses. METHODS: Only patients with good compliance, who used cortisone acetate (CA) during childhood and dexamethasone after the final height achievement. Cumulative GC/MC doses were calculated from diagnosis until last evaluation. BMD was analyzed by the first and last energy X-ray absorptiometry (DXA) scans performed. RESULTS: Twenty simple virilizing (SV) and 14 salt wasting (WS) whose mean age was 26 ± 6 years, mean CA, dexamethasone, and fludrocortisone cumulative doses were 63,813 ± 32,767, 812 ± 558, and 319 ± 325 mg/m2, respectively. Based on the last DXA, low BMD was observed in 11% of patients, total hip Z-score was lower in the SW than SV form (p = 0.04). Cumulative CA dose had an inverse correlation with femoral neck Z-score (p < 0.01). Total cumulative GC and MC doses had an inverse correlation with total hip Z-score (p < 0.01). In the analysis of sequential BMD during dexamethasone therapy, no association was observed among cumulative GC/MC doses, clinical forms, sex, and lumbar Z-score delta. CONCLUSIONS: Even though a low CA regimen during growth periods in addition to MC replacement appears to have an influence on BMD at femoral sites, interestingly a low dexamethasone one does not seem to be deleterious for bone health in adulthood.


Subject(s)
Adrenal Hyperplasia, Congenital , Bone Density , Absorptiometry, Photon , Adrenal Hyperplasia, Congenital/drug therapy , Adult , Child , Glucocorticoids/adverse effects , Humans , Retrospective Studies , Young Adult
7.
Occup Med (Lond) ; 69(3): 189-194, 2019 May 25.
Article in English | MEDLINE | ID: mdl-30882867

ABSTRACT

BACKGROUND: After 5 years' sick leave in Brazil, employees must retire due to disability. The duration from breast cancer surgery to the end of treatment should be ~9 months. However, diagnosis alone can take 6 months. Surveys administered soon after returning to work have highlighted problems regarding the slow speed of the treatment process and lack of protective legislation. AIMS: To assess the barriers and facilitators experienced and the coping strategies adopted by Brazilian women 30 days after return to work following breast cancer treatment. METHODS: A qualitative study of 12 women treated for breast cancer. The interviews were recorded, transcribed verbatim and independently analysed by two researchers using a standardized method of analysis. RESULTS: Women took an average of 583 days to return to work following breast cancer treatment. The return-to-work experience was considered good, with the physical barriers being fatigue and problems with the arms, and the work environmental barriers being related to discrimination from employers and overprotection from colleagues. Facilitators included social and emotional support given by colleagues/relatives/employers and jobs requiring more cognitive effort than physical exertion. Coping strategies were related to job role adjustments and reduction in tasks and working hours. CONCLUSIONS: Results were similar to those reported by previous studies, with the exception of the facilitators. Cognitive effort is commonly considered a barrier. However, the present study had an unusually long duration before return to work, possibly reducing the acute effects of chemotherapy on cognition.


Subject(s)
Breast Neoplasms/rehabilitation , Cancer Survivors/psychology , Cancer Survivors/statistics & numerical data , Occupational Health , Return to Work/statistics & numerical data , Adaptation, Psychological , Adult , Brazil/epidemiology , Female , Humans , Middle Aged , Qualitative Research , Return to Work/psychology , Sick Leave , Social Support , Time Factors , Workplace/psychology
8.
Horm Metab Res ; 48(7): 484-8, 2016 Jul.
Article in English | MEDLINE | ID: mdl-27246621

ABSTRACT

Type 1 insulin-like growth factor receptor (IGF-1R) is overexpressed in a variety of human cancers, including adrenocortical tumors. The aim of the work was to investigate the effects of IGF-1R downregulation in a human adrenocortical cell line by small interfering RNA (siRNA). The human adrenocortical tumor cell line NCI H295R was transfected with 2 specific IGF1R siRNAs (# 1 and # 2) and compared with untreated cells and a negative control siRNA. IGF1R expression was determined by quantitative reverse-transcription PCR (qRTPCR) and Western blot. The effects of IGF-1R downregulation on cell proliferation and apoptosis were assessed. IGF-1R levels were significantly decreased in cells treated with IGF-1R siRNA # 1 or # 2. Relative expression of IGF1R mRNA decreased approximately 50% and Western blot analysis revealed a 30% of reduction in IGF-1R protein. Downregulation of this gene resulted in 40% reduction in cell growth in vitro and 45% increase in apoptosis using siRNA # 2. These findings demonstrate that decreasing IGF-1R mRNA and protein expression in NCI H295R cells can partially inhibit adrenal tumor cell growth in vitro. Targeting IGF1R is a promising therapy for pediatric malignant adrenocortical tumor and can still be an option for adult adrenocortical cancer based on personalized genomic tumor profiling.


Subject(s)
Adrenal Cortex/cytology , Gene Silencing , Receptor, IGF Type 1/metabolism , Apoptosis/genetics , Cell Line , Cell Proliferation , Down-Regulation/genetics , Humans , RNA, Messenger/genetics , RNA, Messenger/metabolism , RNA, Small Interfering/metabolism , Receptor, IGF Type 1/genetics
9.
Genet Mol Res ; 15(1)2016 Jan 29.
Article in English | MEDLINE | ID: mdl-26909937

ABSTRACT

ß-defensins are capable of creating pores in the bacterial membrane. In this study, we aim to determine the structure of 3 different sheep ß-defensin 2 (SBD-2) sequences by molecular modeling. A herd of 47 sheep from the Centre for Ovine and Caprine Research of Pará was selected for this investigation. The AA, AG, and GG alleles were found on ß-defensin sequences. We used homology modeling and molecular dynamic simulations to generate 3D models of peptides and they were successfully validated. The proteins are structurally very similar to classic defensins composed of 3 ß-sheets and 3 disulfide bonds. Variations in the organization of the tertiary structure and distribution of charged residues were found between AA, AG, and GG alleles. In this study, we were able to characterize and show the structure of 3 SBD-2 gene variants for the first time in Amazonian sheep. Results demonstrated that these variants are similar in structures to classic ß-defensins, but contain more positives charges, which may indicate an increase in efficacy.


Subject(s)
Peptides/chemistry , Sheep, Domestic/genetics , beta-Defensins/chemistry , Alleles , Amino Acid Sequence , Animals , Disulfides/chemistry , Gene Expression , Molecular Dynamics Simulation , Molecular Sequence Data , Protein Structure, Secondary , Protein Structure, Tertiary , Sequence Alignment , Sequence Homology, Amino Acid , Static Electricity , beta-Defensins/genetics
10.
Toxicon ; 108: 84-96, 2015 Dec 15.
Article in English | MEDLINE | ID: mdl-26365916

ABSTRACT

This work used eleven Peruvian snake venoms (Bothrops andianus, Bothrops atrox, Bothrops barnetti, Bothrops castelnaudi, Bothriopsis chloromelas, Bothrocophias microphthalmus, Bothrops neuwiedi, Bothriopsis oligolepis, Bothriopsis peruviana, Bothrops pictus and Bothriopsis taeniata) to perform in vitro experimentation and determine its main characteristics. Hyaluronidase (HYAL), phospholipase A2 (PLA2), snake venom metalloproteinase (SVMP), snake venom serine protease (SVSP) and L-amino acid oxidase (LAAO) activities; toxicity by cell viability assays using MGSO3, VERO and HeLa cell lineages; and crossed immunoreactivity with Peruvian (PAV) and Brazilian (BAV) antibothropic polyvalent antivenoms, through ELISA and Western Blotting assays, were determined. Results show that the activities tested in this study were not similar amongst the venoms and each species present their own peculiarities, highlighting the diversity within Bothrops complex. All venoms were capable of reducing cell viability of all tested lineages. It was also demonstrated the crossed recognition of all tested venoms by both antivenoms.


Subject(s)
Antivenins/pharmacology , Bothrops , Crotalid Venoms/toxicity , Animals , Blotting, Western , Brazil , Cell Line , Chlorocebus aethiops , Crotalid Venoms/enzymology , Crotalid Venoms/immunology , Enzyme-Linked Immunosorbent Assay , HeLa Cells , Humans , Hyaluronoglucosaminidase/metabolism , L-Amino Acid Oxidase/metabolism , Metalloproteases/metabolism , Peru , Phospholipases A2/metabolism , Serine Proteases/metabolism , Vero Cells
11.
Osteoporos Int ; 26(6): 1819-23, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25708797

ABSTRACT

UNLABELLED: Adding to the debate around vitamin D's effects on skeletal health, we report the long-term follow-up of two patients with severe vitamin D receptor mutations, who had normal bone mass acquisition and normalization of calcemia around puberty, suggesting that vitamin D might not be essential for skeletal health in adulthood. INTRODUCTION: Vitamin D plays a pivotal role in calcium homeostasis, and the consequences of vitamin D insufficiency for skeletal health, as well as the importance of its supplementation, are a matter of great interest. Individuals bearing homozygous vitamin D receptor (VDR) defects present with severe hypocalcemic rickets in early infancy due to vitamin D resistance. METHODS: Here, we report the follow-up of two patients with hereditary vitamin D-resistant rickets (HVDRR), focusing on bone mass acquisition and evolution of calcemia. RESULTS: Patient 1 is a 30-year-old male bearing a homozygous p.Arg30* nonsense mutation in the VDR DNA-binding domain, who presented at 6 months. From 9 years of age, treatment requirement decreased progressively. Follow-up with DXA showed normal bone mass acquisition. In adulthood, he maintains normocalcemia without calcium supplementation and has no signs of bone fragility. Patient 2 is a 37-year-old female with milder HVDRR and alopecia due to a homozygous p.Gly319Val mutation in the VDR ligand-binding domain. Around puberty, hypercalciuria and kidney stones were detected, resulting in suspension of treatment. Follow-up with DXA revealed normal bone mass, and she maintained normocalcemia without supplementation during gestation and lactation. CONCLUSIONS: The long-term follow-up of HVDRR provides insights into the role of vitamin D in human calcium homeostasis and bone health. The normalization of calcemia and normal bone mass acquisition despite a permanently dysfunctional VDR suggest that vitamin D might not be essential for skeletal health in adulthood. Extrapolation of these findings may have implications in broader clinical settings, especially considering widespread vitamin D supplementation.


Subject(s)
Bone Density/genetics , Hypercalcemia/genetics , Mutation , Receptors, Calcitriol/genetics , Adult , Calcium/blood , Female , Follow-Up Studies , Humans , Hypercalcemia/blood , Male , Pedigree , Rickets/blood , Rickets/genetics
12.
J Frailty Aging ; 4(4): 198-206, 2015.
Article in English | MEDLINE | ID: mdl-27031018

ABSTRACT

BACKGROUND: The epidemiological and nutritional transition processes in the last decades underlie the rising trend of obesity in the elderly and is related to increased risk of chronic non-communicable diseases and decreased functional status. OBJECTIVE: To analyze the association of demographic, socioeconomic, lifestyle and health-related factors with overweight and obesity in elderly. DESIGN: Cross-sectional study. SETTING: Carried out in Campinas-São Paulo, Brazil, in 2011. PARTICIPANTS: 452 non-institutionalized elderly (aged ≥60 years), half were users of a government-run soup kitchen and the other half were neighbors of the same sex. RESULTS: Overweight frequency (BMI ≥25 and <30 kg/m2) was 44.5% and obesity (BMI ≥30 kg/m2) was 21.7%. In the multiple multinomial logistic regression model adjusted for sex, age group and economic class, there was greater chance of overweight among those that reported dyslipidemia; those that reported arthritis/ arthrosis/rheumatism and that once or more per week replaced supper by a snack were more likely to be obese. Elderly who did not leave home daily and reported diabetes had higher chance of overweight and obesity. CONCLUSIONS: Overweight and obesity are associated with worse living and health-related conditions, such as physical inactivity, changes in eating behaviors, and chronic diseases. Public health policies should encourage regular physical activity and healthy eating behaviors, focusing on traditional diet, through nutritional education, in order to reduce the prevalence of overweight and obesity and chronic diseases.

13.
Andrology ; 2(6): 955-66, 2014 Nov.
Article in English | MEDLINE | ID: mdl-25270366

ABSTRACT

The use of clonidine, a selective agonist of α2-adrenoceptors, is related to the fertility impairment. Thus, it has been described that changes in the epididymal function are related to the loss of fertility. Therefore, this study was sought to further evaluate the effects of clonidine in the rat distal cauda epididymis contractions and its consequence in the sperm parameters. The in vitro effects of clonidine in the isolated distal cauda epididymis were evaluated by pharmacological experiments. The consecutive contractile responses for clonidine in distal cauda epididymis showed desensitization. The noradrenaline-induced contractions were desensitized after in vitro clonidine pre-treatment (10(-5) M for 10 min). Clonidine was unable to alter the noradrenaline contractions if the in vitro pre-treatment was made in the presence of idazoxan (α2-adrenoceptor antagonist), whereas prazosin (α1-adrenoceptor antagonist) was ineffective. Moreover, the in vitro clonidine pre-treatment increased frequency and amplitude of spontaneous contraction of distal cauda epididymis. In addition, to induce in vivo desensitization of α2-adrenoceptors, male Wistar rats were treated with crescent doses of clonidine and distal cauda of epididymis contraction and sperm parameters were analyzed. The in vivo treatment with clonidine diminished the potency of the contractions induced by adrenergic agonists and augmented the frequency and amplitude of spontaneous contraction of distal cauda epididymis. This treatment also altered the sperm transit time in epididymis, epididymal sperm reserves, sperm lipid peroxidation, and antioxidant enzymes activity. The results suggest that clonidine was able to affect the sperm quantity and quality by decreasing the transit time related to the increase in the frequency and amplitude of spontaneous contractions in epididymis, although the contractions induced by adrenergic agonists were desensitized.


Subject(s)
Adrenergic alpha-2 Receptor Agonists/pharmacology , Clonidine/pharmacology , Epididymis/drug effects , Spermatozoa/drug effects , Animals , Epididymis/physiology , Male , Muscle Contraction/drug effects , Rats , Rats, Wistar
14.
Peptides ; 59: 42-52, 2014 Sep.
Article in English | MEDLINE | ID: mdl-25017240

ABSTRACT

Honeybee stings are a severe public health problem. Bee venom contains a series of active components, including enzymes, peptides, and biogenic amines. The local reactions observed after envenoming include a typical inflammatory response and pain. Honeybee venom contains some well-known polycationic peptides, such as Melittin, Apamin, MCD peptide, Cardiopep, and Tertiapin. Secapin in honeybee venom was described 38 years ago, yet almost nothing is known about its action. A novel, variant form of this peptide was isolated from the venom of Africanized honeybees (Apis mellifera). This novel peptide, named Secapin-2, is 25 amino acid residues long. Conformational analyses using circular dichroism and molecular dynamics simulations revealed a secondary structure rich in strands and turns, stabilized by an intramolecular disulfide bridge. Biological assays indicated that Secapin-2 did not induce hemolysis, mast cell degranulation or chemotactic activities. However, Secapin-2 caused potent dose-related hyperalgesic and edematogenic responses in experimental animals. To evaluate the roles of prostanoids and lipid mediators in the hyperalgesia and edema induced by this peptide, Indomethacin and Zileuton were used to inhibit the cyclooxygenase and lipoxygenase pathways, respectively. The results showed that Zileuton partially blocked the hyperalgesia induced by Secapin-2 and decreased the edematogenic response. In contrast, Indomethacin did not interfere with these phenomena. Zafirlukast, a leukotriene receptor antagonist, blocked the Secapin-2 induced hyperalgesia and edematogenic response. These results indicate that Secapin-2 induces inflammation and pain through the lipoxygenase pathway in both phenomena.


Subject(s)
Bee Venoms/chemistry , Edema/chemically induced , Hyperalgesia/chemically induced , Animals , Bee Venoms/isolation & purification , Bee Venoms/pharmacology , Bees , Dose-Response Relationship, Drug , Edema/metabolism , Hyperalgesia/metabolism , Male , Mice
15.
Res Vet Sci ; 95(3): 1134-41, 2013 Dec.
Article in English | MEDLINE | ID: mdl-24012348

ABSTRACT

In order to improve the understanding of the toxicity of pentavalent antimony (Sb(V)), we investigated the acute effects of meglumine antimoniate (MA) on the oxidative stress in heart, liver, kidney, spleen and brain tissue of mice. Levels of lipoperoxidation and protein carbonylation were measured to evaluate the oxidative status, whereas superoxide dismutase/catalase activity and glutathione levels were recorded to examine the antioxidative status. We observed that MA caused significant protein carbonylation in the heart, spleen and brain tissue. Increased lipoperoxidation was found in the liver and brain tissue. An imbalance between superoxide dismutase and catalase activities could be observed in heart, liver, spleen and brain tissue. Our results suggest that MA causes oxidative stress in several vital organs of mice. This indicates that the production of highly reactive oxygen and nitrogen species induced by MA might be involved in some of its toxic adverse effects.


Subject(s)
Antiprotozoal Agents/pharmacology , Meglumine/pharmacology , Organometallic Compounds/pharmacology , Oxidative Stress/drug effects , Animals , Antiprotozoal Agents/adverse effects , Brain/drug effects , Brain Chemistry/drug effects , Catalase/metabolism , Glutathione/analysis , Heart/drug effects , Kidney/chemistry , Kidney/drug effects , Lipid Peroxidation/drug effects , Liver/chemistry , Liver/drug effects , Meglumine/adverse effects , Meglumine Antimoniate , Mice , Myocardium/chemistry , Organometallic Compounds/adverse effects , Protein Carbonylation/drug effects , Spleen/chemistry , Spleen/drug effects , Superoxide Dismutase/metabolism
16.
Ann R Coll Surg Engl ; 95(1): 57-60, 2013 Jan.
Article in English | MEDLINE | ID: mdl-23317730

ABSTRACT

INTRODUCTION: Necrotising fasciitis is a life-threatening illness that is often difficult to diagnose. Immediate debridement and intravenous antibiotic therapy are required to limit the spread of infection. This five-year audit aimed to review the number and outcomes of all cases of necrotising fasciitis admitted to a tertiary referral unit and to assess the validity of the Laboratory Risk Indicator for Necrotising Fasciitis (LRINEC) scoring system. METHODS: A retrospective analysis of patient notes over the five-year period from October 2006 to October 2011 was undertaken. The LRINEC score was calculated for each patient to evaluate its usefulness. RESULTS: Overall, 15 patients were diagnosed with necrotising fasciitis. Three patients died. The median age of patients was 51.0 years (range: 34-76 years). There were no obvious predisposing factors in 8 cases but patients had a median of 2.0 co-morbidities. The most common infective agent, present in five patients, was Group A Streptococcus. Other monomicrobial agents included Group G Streptococcus and Klebsiella pneumoniae. Polymicrobial infections were less common than mono-microbial infections and two patients had a polymicrobial infection including methicillin-resistant Staphylococcus aureus. Although the LRINEC scoring system identified 12 of the 15 patients as having a high or intermediate likelihood of necrotising fasciitis, 3 were classified as low likelihood. CONCLUSIONS: This limited case series strongly suggests that the LRINEC system is too insensitive for diagnosis.


Subject(s)
Fasciitis, Necrotizing/diagnosis , Severity of Illness Index , Adult , Aged , Anti-Bacterial Agents/therapeutic use , Debridement/statistics & numerical data , Early Diagnosis , Fasciitis, Necrotizing/microbiology , Fasciitis, Necrotizing/therapy , Female , Hospital Mortality , Humans , Immunoglobulins, Intravenous/therapeutic use , Male , Middle Aged , Retrospective Studies , Sensitivity and Specificity , Time-to-Treatment
17.
Rev. paul. pediatr ; 29(2): 239-244, June 2011. tab
Article in Portuguese | LILACS | ID: lil-594005

ABSTRACT

OBJETIVOS: Analisar o Inventário de Percepção Neonatal de Broussard, um instrumento que detecta as percepções e expectativas maternas com respeito aos filhos logo após o parto (Tempo 1) e com um mês de vida (Tempo 2), em puérperas multíparas e primíparas. MÉTODOS: Coorte prospectiva com 27 multíparas e 29 primíparas mães de neonatos a termo saudáveis. Inquiriu-se à mãe no segundo dia pós-parto quanta dificuldade ela esperava que a maioria dos bebês tivesse em relação a chorar, alimentar, regurgitar ou vomitar, evacuar, dormir e ter uma rotina. As respostas foram marcadas em uma escala de 5 pontos. A seguir, repetiam-se as perguntas em relação ao seu filho recém-nascido. Após 30 dias, perguntava-se à mãe quanta dificuldade ela achava que a maioria dos bebês e seu próprio filho apresentavam em relação aos mesmos quesitos. A análise estatística utilizou ANOVA para medidas repe-tidas, considerando os seguintes efeitos principais: tempo, grupo (primíparas e multíparas) e categoria (seu bebê e a maioria dos bebês). RESULTADOS: Logo após o parto, as mães esperavam que seus filhos tivessem menos dificuldade nas atividades avalia-das do que a maioria dos bebês. Essa expectativa se confirmou com 30 dias de vida para todos os comportamentos. Não houve diferenças entre primíparas e multíparas. CONCLUSÕES: O Inventário de Percepção Neonatal de Broussard foi bem entendido e aceito pelas mães, mostrando resultados consistentes neste estudo. O instrumento pode ser útil para triar pares mãe-bebê com dificuldades no estabelecimento de vínculo.


OBJECTIVES: To evaluate Broussard's Neonatal Perception Inventory (BPNI), an instrument to measure the mother's perception and expectations regarding her newborn infant at immediate postpartum and one month afterwards in primiparous and multiparous women. METHODS: Prospective cohort of 27 multiparous and 29 primiparous mothers of healthy newborn infants. In the second day postpartum, mothers were asked about the difficulties they thought that babies would offer regarding specific behaviors: crying, spitting, feeding, elimination, sleeping and predictability. Answers were rated in a 5-point scale. Next, mothers were questioned about their own babies regarding the same items. After 30 days, the mothers were questioned again about her perception of most babies and their own baby regarding the same items. The results were analyzed by repeated measures ANOVA considering the following main effects: time, group (primiparous and mul-tiparous), and subjects (mother's baby and most babies). RESULTS: Following birth, mothers expected their babies to have fewer difficulties in the daily activities than the ma-jority of the babies. These expectations were confirmed one month later for all items. There were no differences between primiparous and multiparous mothers. CONCLUSIONS: The Broussard's Neonatal Perception In-ventory was well understood and accepted by mothers and showed consistent results in this study. It can be used as a screening psychological tool to assess bonding between mothers and infants.


OBJETIVOS: Analizar el Inventario de Percepción Neonatal de Broussard (BNPI - un instrumento que detecta las percepciones y expectativas maternas respecto a los hijos) enseguida al parto (T1) y con un mes de vida (T2), en puér-peras multíparas y primíparas. MÉTODOS: Coorte prospectiva con 27 multíparas y 29 primíparas madres de neonatos a término sanos. Se preguntó a la madre en T1 la dificultad que ella esperaba que la mayoría de los bebés tuviera respecto a llorar, alimentarse, regurgitar o vomitar, evacuar, dormir y tener una rutina. Las respuestas fueron marcadas en una escala de 5 puntos. Enseguida, se repitieron las preguntas respecto a su hijo recién-nacido. En T2, se preguntaba a la madre la dificultad que ella creía que la mayoría de los bebés y su propio hijo presentaban respecto a los mismos requisitos. El análisis estadístico utilizó ANOVA para medidas repetidas, teniendo en cuenta los siguientes efectos principales: tiempo (T1 y T2), grupo (primíparas y multíparas) y categoría (su bebé y la mayoría de los bebés). RESULTADOS: Enseguida al parto, las madres esperaban que sus hijos tuvieran menos dificultad en las actividades evaluadas que la mayoría de los bebés. Esta expectativa se confirmó con 30 días de vida para todos los comportamientos. No hubo diferencias entre primíparas y multíparas. CONCLUSIONES: El BNPI fue bien atendido y aceptado por las madres, mostrando resultados consistentes en este estudio. El instrumento puede ser útil para seleccionar pares madre-bebé con dificultades en el establecimiento de vínculo.


Subject(s)
Humans , Infant, Newborn , Object Attachment , Cohort Studies , Mother-Child Relations , Maternal and Child Health
18.
Amino Acids ; 40(1): 101-11, 2011 Jan.
Article in English | MEDLINE | ID: mdl-20177946

ABSTRACT

Stings by bees and wasps, including Brazilian species, are a severe public health problem. The local reactions observed after the envenoming includes typical inflammatory response and pain. Several studies have been performed to identify the substances, including peptides that are responsible for such phenomena. The aim of the present study is to characterize the possible nociceptive (hyperalgesic) and edematogenic effects of some peptides isolated from the venoms of the honeybee (Apis mellifera) and the social wasps Polybia paulista and Protonectarina sylveirae, in addition to characterize some of the mechanisms involved in these phenomena. For this purpose, different doses of the peptides mellitin (Apis mellifera), Polybia-MP-I, N-2-Polybia-MP-I (Polybia paulista), Protonectarina-MP-NH2 and Protonectarina-MP-OH (Protonectarina sylveirae) were injected into the hind paw of mice. Hyperalgesia and edema were determined after peptide application, by using an electronic von Frey apparatus and a paquimeter. Carrageenin and saline were used as controls. Results showed that melittin, Polybia-MP-I, N-2-Polybia-MP-I, Protonectarina-MP-NH(2) and Protonectarina-MP-OH peptides produced a dose- and time-related hyperalgesic and edematogenic responses. Both phenomena are detected 2 h after melittin, Polybia-MP-I, N-2-Polybia-MP-I injection; their effects lasted until 8 h. In order to evaluate the role of prostanoids and the involvement of lipidic mediators in hyperalgesia induced by the peptides, indomethacin and zileuton were used. Results showed that zileuton blocked peptide-induced hyperalgesia and induced a decrease of the edematogenic response. On the other hand, indomethacin did not interfere with these phenomena. These results indicate that melittin, Polybia-MP-I, N-2-Polybia-MP-I, Protonectarina-MP-NH(2), and Protonectarina-MP-OH peptides could contribute to inflammation and pain induced by insect venoms.


Subject(s)
Bee Venoms/adverse effects , Bees/chemistry , Bites and Stings/chemically induced , Edema/chemically induced , Hyperalgesia/chemically induced , Wasp Venoms/adverse effects , Animals , Bee Venoms/immunology , Bee Venoms/isolation & purification , Bites and Stings/immunology , Edema/immunology , Humans , Hyperalgesia/immunology , Male , Mice , Pain/chemically induced , Pain/immunology , Wasp Venoms/immunology , Wasp Venoms/isolation & purification , Wasps/chemistry
19.
Dentomaxillofac Radiol ; 39(8): 494-500, 2010 Dec.
Article in English | MEDLINE | ID: mdl-21062943

ABSTRACT

OBJECTIVES: The aims of this study were to evaluate the visibility of the lateral pterygoid muscle (LPM) in temporomandibular joint (TMJ) images obtained by MRI, using different projections and to compare image findings with clinical symptoms of patients with and without temporomandibular disorders (TMD). METHODS: In this study, LPM images of 50 participants with and without TMDs were investigated by MRI. The images of the LPM in different projections of 100 TMJs from 35 participants (70 TMJs) with and 15 participants (30 TMJs) without clinical signs and symptoms of TMD were visible and analysed. RESULTS: The oblique sagittal and axial images of the TMJ clearly showed the LPM. Hypertrophy (1.45%), atrophy (2.85%) and contracture (2.85%) were the abnormalities found in the LPM. TMD signs, such as hypermobility (11.4%), hypomobility (12.9%) and disc displacement (20.0%), could be seen in TMJ images. Related clinical symptoms, such as pain (71.4%), articular sounds (30.4%), bruxism (25.7%) and headache (22.9%), were observed. CONCLUSIONS: Patients with TMD can present with alterations in the LPM thickness. Patients without TMD also showed alterations, such as atrophy and contracture, in TMJ images. Recognition of alterations in the LPM will improve our understanding of clinical symptoms and pathophysiology of TMD, and may lead to a more specific diagnosis of these disorders.


Subject(s)
Magnetic Resonance Imaging/methods , Pterygoid Muscles/pathology , Temporomandibular Joint Dysfunction Syndrome/pathology , Case-Control Studies , Chi-Square Distribution , Contracture/pathology , Female , Humans , Joint Dislocations/pathology , Joint Instability/pathology , Male , Muscular Atrophy/pathology , Prospective Studies , Range of Motion, Articular , Temporomandibular Joint/pathology
20.
Rev. paul. pediatr ; 27(1): 6-14, mar. 2009. graf, tab
Article in Portuguese | LILACS | ID: lil-511860

ABSTRACT

OBJETIVO: Analisar comparativamente a incidência e o perfil etiológico da infecção hospitalar em recém-nascidos (RN) de origem interna e externa, admitidos em Unidade de Terapia Intensiva Neonatal (UTIN). MÉTODOS: Estudo de coorte em RN internados na UTIN em 2002 e 2003. A vigilância epidemiológica das infecções hospitalares foi realizada prospectivamente, seguindo-se os métodos do National Nosocomial Infections Surveillance System. Compararam-se as características clínicas, demográficas, a incidência de infecção hospitalar precoce e tardia e o perfil dos microrganismos isolados dos RN com infecção tardia, segundo o local de nascimento. RESULTADOS: Incluíram-se no estudo 426 RN de origem interna (88%) e 60 de origem externa (12%). A incidência de infecção hospitalar precoce foi 10% e tardia, 21%, sem diferença estatística entre os RN internos e externos quanto à ocorrência de infecção hospitalar precoce (p=0,40) e tardia (p=0,41). Entre os micro-organismos isolados na infecção tardia, 52% foram Gram-positivos, com predomínio do Staphylococcus coagulase negativo, tanto para as infecções em RN externos (33%) quanto internos (41%). Dentre os Gram-negativos, Pseudomonas spp. e Enterobacter spp. foram isolados com maior frequência nos RN externos. A sepse (54%) e a pneumonia (20%) foram as infecções mais frequentes. CONCLUSÕES: Entre os grupos de RN separados de acordo com o local de nascimento, não houve diferença na incidência de infecção hospitalar precoce e tardia e no agente etiológico predominante da infecção hospitalar tardia.


OBJECTIVE: To analyze the hospital infection incidence rate and their etiologic profile among inborn and outborn infants admitted to a Neonatal Intensive Care Unit (NICU). METHODS: This cohort study included newborns admitted to a NICU in 2002 and 2003. Hospital infection epidemiologic surveillance was conducted prospectively following the National Nosocomial Infections Surveillance System methodology. Clinical and demographic aspects, early and late hospital infection incidence rates, and the organisms isolated from newborns with late hospital infection were compared according to birth place. RESULTS: In this study, 426 (88%) inborn and 60 (12%) outborn infants were included. Early and late onset hospital infection incidence rate were 10% and 21% respectively, with no statistical difference between inborn and outborn infants for early (p=0.40) and late hospital infections (p=0.41). Among the microorganisms isolated in late hospital infections, 52% were Gram-positive organisms: coagulase-negative Staphylococcus was the predominant bacteria for outborn (33%) and inborn infants (41%). Among Gram-negative organisms, Pseudomonas spp. and Enterobacter spp. were more prevalent in outborn infants. Sepsis (54%) was the most frequent infection, followed by pneumonia (20%). CONCLUSIONS: No statistical difference was verified between inborn and outborn infants regarding early or late hospital infection incidence rates and the main etiologic agents isolated from infants with late hospital infection.


Subject(s)
Humans , Male , Female , Infant, Newborn , Cross Infection/epidemiology , Intensive Care, Neonatal
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