ABSTRACT
This study aimed to assess the influence of glycosaminoglycan (chondroitin and glucosamine sulfates) supplementation in the diet of broilers on the expression of matrix metallopeptidase 9 (MMP-9) and metallopeptidase inhibitor 2 (TIMP-2) genes, the synthesis of proteoglycans, collagen type II and chondrocytes, bone and cartilage macroscopy, bone mineral densitometry, bone breaking strength and mineral profile. A completely randomized design was carried out in a 3 × 3 factorial scheme (3 levels of chondroitin sulfate: 0.00, 0.05, and 0.10%; and 3 levels of glucosamine sulfate: 0.00, 0.15, and 0.30%), totaling 9 treatments. At 21 and 42 d of age, broilers were slaughtered, and tibias and femurs were collected for evaluation. There was an interaction (P < 0.05) of sulfates for the expression of MMP-9 and its inhibitor TIMP-2 in femur articular cartilage, as well as for the number of chondrocytes, collagen type II and proteoglycans in tibia articular cartilage, bone and cartilage macroscopy and mineral profile (P < 0.05), with better results obtained with the inclusion of chondroitin and/or glucosamine sulfates in the feed. In conclusion, chondroitin and glucosamine sulfates can be used in broiler diets in order to favor the development of the structure of the locomotor system (bones and joints), thus preventing locomotion problems.
Subject(s)
Cartilage, Articular , Glycosaminoglycans , Animals , Glycosaminoglycans/metabolism , Tissue Inhibitor of Metalloproteinase-2/metabolism , Tissue Inhibitor of Metalloproteinase-2/pharmacology , Chickens , Collagen Type II/metabolism , Collagen Type II/pharmacology , Matrix Metalloproteinase 9/metabolism , Matrix Metalloproteinase 9/pharmacology , Proteoglycans/genetics , Proteoglycans/metabolism , Chondroitin Sulfates/metabolism , Chondroitin Sulfates/pharmacology , Glucosamine/metabolism , Glucosamine/pharmacology , Minerals/metabolism , Sulfates/metabolismABSTRACT
The growth and development of organisms depend on nutrient availability. Dermatophytes must sense nutrient levels and adapt to the host environment to colonize human and animal keratinized tissues. Owing to the clinical importance of the Trichophyton genus, this study compared the expression profile of genes involved in metabolism, cell cycle control, and proteases in two Trichophyton species, Trichophyton rubrum, and Trichophyton interdigitale, in response to nutrients and environmental pH. In addition, we evaluated the activity of enzymes in the tricarboxylic acid, glyoxylate, and methylcitrate cycles. Moreover, the effects of interruption of the transcription factor pacC on T. interdigitale in the same conditions as for the wild-type strain were determined. Our analyses revealed specific responses in each species to the nutritional and pH variation. An improved adaptation of T. interdigitale to keratin was observed, compared with that of T. rubrum. T. rubrum growth in buffered keratin media indicated pH 8.0 as an optimal pH condition for metabolic activity, which differed from that for T. interdigitale. Tricarboxylic acid components in T. rubrum showed increased enzymatic activity and transcript accumulation. In T. interdigitale, a higher activity of enzymes in glyoxylate and methylcitrate cycles was observed, with no direct correlation to the transcriptional profile. T. interdigitale fungal metabolism suggests the requirement of anaplerotic pathways in the late cultivation period. The identified differences between T. rubrum and T. interdigitale may represent determinants for adaptation to the host and the incidence of infection with each species.
ABSTRACT
BACKGROUND: Hydroxychloroquine has shown potential to block viral replication of SARS-CoV-2 in some in vitro studies. This randomised, double-blinded, placebo controlled clinical trial evaluated the efficacy of hydroxychloroquine plus azithromycin (HCQ/AZT) in reducing viral loads in patients with early and mild SARS-CoV-2 infection. METHODS: A single-centre randomised placebo-controlled clinical trial was conducted with outpatients with early and mild SARS-CoV-2 infection. Inclusion criteria were: patients aged 18-65 years with symptoms suggestive of COVID-19 for < 5 days, no significant comorbidities, and positive nasopharyngeal/oropharyngeal swab screening tests (POCT-PCR). Randomised patients received either hydroxychloroquine for 7 days plus azithromycin for 5 days or placebo. The primary endpoint was viral clearance within a 9-day period. Secondary endpoints included viral load reduction, clinical evolution, hospitalization rates, chest computed tomography evolution, and adverse effects. RESULTS: From 107 potential trial participants, 84 were enrolled following predetermined criteria. Statistical analyses were performed on an intention-to-treat (N = 84) and per-protocol (PP) basis (N = 70). On the PP analysis, the treatment (N = 36) and placebo (N = 34) groups displayed similar demographic characteristics. At 95% CI, no statistically significant between-group differences were found in viral clearance rates within 9 days following enrolment (P = 0.26). CONCLUSIONS: This randomised, double-blinded, placebo-controlled clinical trial evaluating outpatients with early and mild COVID-19 showed that viral clearance rates within a 9-day period from enrolment did not change with HCQ/AZT treatment compared with placebo, although no major cardiovascular events were observed in participants without comorbidities. Secondary outcomes were also not significantly improved with HCQ/AZT treatment compared with placebo. These findings do not support use of HCQ/AZT in this setting.
Subject(s)
Antiviral Agents/therapeutic use , Azithromycin/therapeutic use , COVID-19 Drug Treatment , Hydroxychloroquine/therapeutic use , Adult , COVID-19/etiology , Double-Blind Method , Female , Humans , Male , Middle Aged , Outpatients , Placebos , Treatment Outcome , Viral LoadABSTRACT
BACKGROUND: Systemic arterial hypertension (SAH) is a multifactorial condition that already affects one third of the worldwide population. The identification of candidate genes for hypertension is a challenge for the next years. Nevertheless, the small contribution of each individual genetic factor to the disease brings the necessity of evaluate genes in an integrative manner and taking into consideration the physiological interaction of functions. Angiotensin I-converting enzymes, ACE and ACE2, are key regulators of blood pressure that have counterbalance roles by acting on vasoactive peptides from Renin-Angiotensin-Aldosterone System (RAAS). Insertion/deletion (I/D) polymorphism of ACE gene and single nucleotide polymorphism G8790A of ACE2 gene have been associated with susceptibility to SAH, but the literature is controversial. We proposed to evaluate these two polymorphisms jointly exploring the combined effects of ACE and ACE2 genotypes on SAH susceptibility, an approach that have not been done yet for ACE and ACE2 polymorphisms. METHODS AND FINDINGS: This genetic association study included 117 hypertensive (mean age 59.7 years) patients and 123 normotensive and diabetes-free controls (mean age 57.5 years). ACE and ACE2 polymorphisms were genotyped by SYBR Green real-time PCR and RFLP-PCR, respectively. Crude and adjusted odds ratio (OR) values were calculated to estimate the susceptibility to SAH development. It was obtained homogeneity regarding distribution by sex, age range, smoking, alcohol consumption and body mass index (BMI) between case and control groups. No-association was verified for each gene individually, but the combination of ACE and ACE2 polymorphisms on female gender revealed a significative association for DD/G_ carriers who had a 3-fold increased risk to SAH development (p = 0.03), with a stronger susceptibility on DD/GG carriers (7-fold increased risk, p = 0.01). The D allele of ACE showed association with altered levels of lipid profile variables on case group (VLDL-cholesterol, p = 0.01) and DD genotype in all individuals analysis (triglycerides, p = 0.01 and VLDL-cholesterol, p = 0.01). CONCLUSION: These findings indicate that the combination of ACE and ACE2 polymorphisms effects may play a role in SAH predisposition been the DD/G_ genotype the susceptibility profile. This result allowed us to raise the hypothesis that an increased activity of ACE (prohypertensive effects) in conjunction with reduced ACE2 activity (antihypertensive effects) could be the underlining mechanism. The association of ACE D allele with lipid alterations indicate that this can be a marker of poor prognostic on SAH evolution and contribute to CVD development. Although these preliminary findings must be confirmed by further researches with larger sample size, we could observe that the integrative analysis of ACE and ACE2 can be an informative tool in hypertension understanding that needs to be explored in new studies.
Subject(s)
Dyslipidemias/epidemiology , Genetic Predisposition to Disease , Hypertension/genetics , Peptidyl-Dipeptidase A/genetics , Adult , Age Factors , Aged , Aged, 80 and over , Alleles , Angiotensin-Converting Enzyme 2 , Blood Pressure/genetics , Brazil/epidemiology , Case-Control Studies , Dyslipidemias/genetics , Female , Follow-Up Studies , Gene Frequency , Genetic Association Studies , Humans , Hypertension/epidemiology , INDEL Mutation , Male , Middle Aged , Polymorphism, Single Nucleotide , Risk Factors , Sex Factors , Young AdultABSTRACT
The dimorphic fungi Paracoccidioides spp. are the etiological agents of paracoccidioidomycosis (PCM), a prevalent systemic mycosis in Latin America. The Paracoccidioides lutzii response to oxidative stress is largely unexplored. Thioredoxins (TRX) are involved in the regulation of the redox environment in the cell, responding to oxidative stress in several organisms. In this study, we describe the isolation and characterization of a cDNA encoding a thioredoxin 1 from yeast cells from P. lutzii. The cDNA codes for a 12kDa protein containing the characteristic thioredoxin active site. The thioredoxin 1 gene was expressed in Escherichia coli and the isolated thioredoxin 1 recombinant protein as the native PlTRX1 from yeast cells showed insulin reduction activity in vitro. We also showed by semi-quantitative RT-PCR analysis that the expression of thioredoxin 1 gene was induced in response to H2O2 and may exert an antioxidant activity in vivo. Our results suggest that the thioredoxin 1 may play an important role in controlling the redox status in P. lutzii which may contribute to this organism's virulence.
Subject(s)
Fungal Proteins/genetics , Fungal Proteins/metabolism , Gene Expression Regulation, Fungal , Insulin/metabolism , Paracoccidioides/genetics , Thioredoxins/genetics , Thioredoxins/metabolism , Amino Acid Sequence , Base Sequence , Cloning, Molecular , DNA, Complementary/genetics , Escherichia coli/genetics , Fungal Proteins/chemistry , Gene Expression , Gene Expression Regulation, Fungal/drug effects , Hydrogen Peroxide/pharmacology , Paracoccidioides/drug effects , Phylogeny , Thioredoxins/chemistryABSTRACT
Os atuais sistemas de criação de equinos estão associados às dietas ricas em carboidratos que resultam em sobre peso e acúmulo de gordura em animais ainda muito jovens. Nesses animais com sobre peso submetidos exercício físico intenso há aumento na incidência de osteoartrite juvenil e outras afecções inflamatórias. O objetivo deste estudo foi associar a adiposidade corporal e a forma de criação de potros com o perfil energético sanguíneo, as concentrações sanguíneas de proteínas inflamatórias e lesões osteoarticulares na região társica comparando animais criados em regimes intensivo ou extensivo. Foram avaliados 40 potros com 18 meses de idade da raça crioula, 23 fêmeas e 17 machos, sendo 20 animais criados exclusivamente em sistema extensivo e 20 animais criados em sistema intensivo. Foram efetuadas coletas de sangue para avaliação bioquímica e eletroforese proteica. Foram efetuadas através de ultrassonografia a mensuração da gordura na crista do pescoço, região retroperitoneal e na base da cauda. Em 17 animais do grupo intensivo e nove animais do grupo extensivo foi efetuado o estudo radiográfico da região do tarso esquerdo. Foi observado maiores níveis de colesterol total e LDL, glicemia, Amilóide A sérica (SAA), transferrina, haptoglobina, ceruloplasmina, glicoproteína ácida e uma proteína de 23Kda de peso molecular (não identificada) nos animais do grupo intensivo com relação aos do grupo extensivo. O grupo intensivo também apresentou maior depósito de gordura na região da crista do pescoço, região retroperitoneal e base da cauda. Em 100% dos animais do grupo intensivo foram observados lesões compatíveis com osteoartrite juvenil, enquanto que em apenas 23% dos animais do grupo extensivo apresentaram tais alterações. No teste exato de Fisher foi observado que os animais do grupo intensivo apresentaram 105% mais chance de desenvolver osteoartrite que os animais do grupo extensivo. Ainda, no teste de Pearson foi observada correlação positiva entre a gordura na crista do pescoço com o grau de comprometimento articular dos potros. A gordura na crista do pescoço apresentou correlação positiva com as alterações osteoarticulares, com os níveis séricos de colesterol LDL, níveis séricos de glicose, níveis de glicoproteína ácida, haptoglobina, transferrina e SAA. A SAA apresentou correlação com a espessura de gordura retroperitoneal. Conclui-se que o depósito de gordura na crista do pescoço apresenta correlação com as alterações no perfil energético, inflamatório e no comprometimento osteoarticular dos animais avaliados. Os níveis de glicose, colesterol LDL, glicoproteína ácida, haptoglobina, ceruloplasmina, transferrina e SAA estiveram correlacionados ao depósito de gordura na crista do pescoço. Potros em sistema intensivo apresentam, em relação aos criados em sistema extensivo, 105 % mais chance de apresentarem lesões articulares degenerativas crônicas compatíveis com osteoartrite juvenil.(AU)
High carbohydrate diets are increasingly used in horse rearing systems. This can result in weight gain and fat accumulation in young horses. There is a growing incidence of juvenile osteoarthritis and other inflammatory conditions in overweight young horses that undergo intense physical exercise. The aim of this study was to associate corporal adiposity with energy profile, serum concentration of acute phase proteins and presence of osteo-articular lesion in the tarsal region of young horses raised in two different rearing systems: intensive system and extensive system. We evaluated 40 young horses 18 months old, 23 of them were females and 17 were males. Twenty horses were raised in the extensive rearing system and twenty horses were raised in intensive rearing system. Blood samples were collected for biochemical analysis and protein electrophoresis. Fat deposition on the crest of the neck, peritoneum and tailhead was measured by ultrasonography. Radiographic examination of the left tarsus was performed in 17 horses of the farm rearing system and in nine horses of the extensive rearing system. We observed higher levels of total cholesterol, LDL, glucose, serum amyloid A (SAA), transferrin, haptoglobin, acid glycoprotein and unidentified protein 23Kda in horses of the intensive system. These horses also showed higher fat deposition on the crest of the neck, peritoneum and tailhead than horses raised on extensive system. All horses on the intensive system group that underwent radiographic examination had lesions compatible with juvenile osteoarthritis while only 23% of the animals of the extensive system group showed such changes. With Fisher's exact test we observed that horses of the intensive rearing system are 105% more likely to develop osteoarthritis than horses of the extensive rearing system. With the Pearson correlation test we found a positive correlation between fat deposition on the crest of the neck and degree of articular injury. Fat deposition on the crest of the neck also showed a positive correlation with serum levels of LDL, glucose, acid glycoprotein, haptoglobin, transferrin and SAA. The SAA correlated with the thickness of retroperitoneal fat. There was a positive correlation between retroperitoneal fat deposition and presence of osteoarticular abnormalities. In conclusion, fat deposition on the crest of the neck has a correlation with energetic profile changes, cute phase proteins changes and with articular injuries. Levels of glucose, LDL cholesterol, acid glycoprotein, haptoglobin, ceruloplasmin, transferrin and SAA have a correlation with fat deposition on the crest of the neck. In addition, young horses of the intensive rearing system are 105% more likely to have chronic degenerative joint lesions compatible with juvenile osteoarthritis than horses of the extensive rearing system.(AU)
Subject(s)
Animals , Acute-Phase Reaction/veterinary , Adiposity , Horses/blood , Horses/physiology , Joints/injuries , Obesity , Osteoarthritis/veterinary , Proteins/analysisABSTRACT
In this article, the experiments used to construct the ambient pH-signaling network involved in the secretion of enzymes by filamentous fungi have been reviewed, focusing on the phosphate-repressible phosphatases in Aspergillus nidulans. Classic and molecular genetics have been used to demonstrate that proteolysis of the transcription factor PacC at alkaline ambient pH is imperative for its action, implying that the full-length version is not an active molecular form of PacC. It has been hypothesized that the transcriptional regulator PacC may be functional at both acidic and alkaline ambient pH, in either the full-length or the proteolyzed form, if it carries a pal-dependent molecular tag. The products of the pal genes are involved in a metabolic pathway that led to the synthesis of effector molecules that tag the pacC product, perhaps facilitating its proteolysis.
Subject(s)
Aspergillus nidulans/enzymology , Fungal Proteins/physiology , Phosphates/metabolism , Transcription Factors/physiology , Aspergillus nidulans/genetics , Fungal Proteins/metabolism , Gene Expression Regulation, Fungal , Hydrogen-Ion Concentration , Models, Biological , Models, Chemical , Phosphoric Monoester Hydrolases/metabolism , Signal Transduction/physiology , Transcription Factors/metabolismABSTRACT
In fungi, ambient pH sensing involves the activation of the Pal/PacC signalling pathway. In the dermatophyte Trichophyton rubrum, pH-dependent secretion of keratinases, which are major virulence determinants, is affected by disruption of the pacC gene. Here, the transcription profiling of the genes coding for N- and O-linked mannosyltransferases, enzymes involved in protein glycosylation, was evaluated in T. rubrum in response to disruption of the pacC gene and growth in keratin, glucose, and glucose plus glycine. We show that transcription of these mannosyltransferase genes is affected by nutrients at acidic pH and by PacC.
ABSTRACT
The examination of entomological collections of cicadas of several Brazilian institutions revealed three undescribed species in the genus Fidicinoides Boulard & Martinelli i.e., F. dolosa sp.n., F. carmenae sp.n. and F. rosabasalae sp.n. They are described and illustrated based on the male genitalia, the right anterior femur and the operculum.
Subject(s)
Hemiptera/anatomy & histology , Hemiptera/classification , Animals , Brazil , MaleABSTRACT
O exame de coleções entomológicas de cigarras de diversas instituições brasileiras revelou três novas espécies do gênero Fidicinoides Boulard & Martinelli, i.e., F. dolosa sp.n., F. carmenae sp.n. e F. rosabasalae sp.n. Estas foram descritas e ilustradas, baseando-se na genitália masculina, fêmur direito e o opérculo.
The examination of entomological collections of cicadas of several Brazilian institutions revealed three undescribed species in the genus Fidicinoides Boulard & Martinelli i.e., F. dolosa sp.n., F. carmenae sp.n. and F. rosabasalae sp.n. They are described and illustrated based on the male genitalia, the right anterior femur and the operculum.
Subject(s)
Animals , Male , Hemiptera/anatomy & histology , Hemiptera/classification , BrazilABSTRACT
The rubber tree lace bug, Leptopharsa heveae Drake & Poor occurs in high populations in rubber tree plantations and it is a limiting factor in rubber production due to the loss of photosynthetic tissue. The control of the pest has been made mainly with chemical products, which cause environmental contamination. The alternative would be the use of biological control agents, however, information about L. heveae natural enemies are scarce. The parasitoid Erythmelus tingitiphagus (Soares) parasitize eggs of the rubber tree lace bug. The aim of this study was to verify the occurrence of E. tingitiphagus in plantations of several rubber tree clones, located in Itiquira town, Mato Grosso State. The plant leaflets of the clones RRIM 600, PR 255, GT 1, PB 235 and PB 217 were collected weekly from October 2005 to February 2006. Parasitism was recorded during the entire study period. The parasitism rate of L. heveae eggs in the different clones ranged from 16.8 to 20.6%.
Subject(s)
Hemiptera/parasitology , Hevea/parasitology , Hymenoptera/physiology , Animals , Ovum/parasitologyABSTRACT
The rubber tree lace bug, Leptopharsa heveae Drake & Poor occurs in high populations in rubber tree plantations and it is a limiting factor in rubber production due to the loss of photosynthetic tissue. The control of the pest has been made mainly with chemical products, which cause environmental contamination. The alternative would be the use of biological control agents, however, information about L. heveae natural enemies are scarce. The parasitoid Erythmelus tingitiphagus (Soares) parasitize eggs of the rubber tree lace bug. The aim of this study was to verify the occurrence of E. tingitiphagus in plantations of several rubber tree clones, located in Itiquira town, Mato Grosso State. The plant leaflets of the clones RRIM 600, PR 255, GT 1, PB 235 and PB 217 were collected weekly from October 2005 to February 2006. Parasitism was recorded during the entire study period. The parasitism rate of L. heveae eggs in the different clones ranged from 16.8 to 20.6 percent.
O percevejo-de-renda, Leptopharsa heveae Drake & Poor ocorre em altas populações em plantios de seringueira, sendo fator limitante para a extração de látex devido à perda de área fotossintetizante. O controle da praga tem sido principalmente à base de produtos fitossanitários, o que gera contaminação ambiental. A alternativa para o uso de inseticidas seria a utilização de agentes de controle biológico, entretanto, informações acerca dos inimigos naturais de L. heveae são escassas. O parasitóide Erythmelus tingitiphagus (Soares) ocorre parasitando ovos do percevejo-de-renda. O objetivo deste estudo foi verificar a ocorrência de E. tingitiphagus em plantios de vários clones de seringueira, no município de Itiquira, MT. Foram coletados semanalmente folíolos de plantas dos clones RRIM 600, PR 255, GT 1, PB 235 e PB 217, de outubro de 2005 a fevereiro de 2006. Observou-se a ocorrência do parasitóide durante todo o período estudado. A taxa de parasitismo de ovos de L. heveae hospedados nos diferentes clones variou de 16,8 a 20,6 por cento.