Impaired signaling pathways on Berardinelli-Seip congenital lipodystrophy macrophages during Leishmania infantum infection.

Berardinelli-Seip congenital lipodystrophy (CGL), a rare autosomal recessive disorder, is characterized by a lack of adipose tissue. Infections are one of the major causes of CGL individuals' premature death. The mechanisms that predispose to infections are poorly understood. We used Leishmania infantum as an in vitro model of intracellular infection to explore mechanisms underlying the CGL infection processes, and to understand the impact of host mutations on Leishmania survival, since this pathogen enters macrophages through specialized membrane lipid domains. The transcriptomic profiles of both uninfected and infected monocyte-derived macrophages (MDMs) from CGL (types 1 and 2) and controls were studied. MDMs infected with L. infantum showed significantly downregulated expression of genes associated with infection-response pathways (MHC-I, TCR-CD3, and granzymes). There was a transcriptomic signature in CGL cells associated with impaired membrane trafficking and signaling in response to infection, with concomitant changes in the expression of membrane-associated genes in parasites (e.g. δ-amastins). We identified pathways suggesting the lipid storage dysfunction led to changes in phospholipids expression and impaired responses to infection, including immune synapse (antigen presentation, IFN-γ signaling, JAK/STAT); endocytosis; NF-kappaB signaling; and phosphatidylinositol biosynthesis. In summary, lipid metabolism of the host plays an important role in determining antigen presentation pathways.

SARS-CoV-2 reinfections with BA.1 (Omicron) variant among fully vaccinated individuals in northeastern Brazil.

BACKGROUND: The first case of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection in Rio Grande do Norte, northeastern Brazil, was diagnosed on March 12, 2020; thereafter, multiple surges of infection occurred, similar to what was seen elsewhere. These surges were mostly due to SARS-CoV-2 mutations leading to emergence of variants of concern (VoC). The introduction of new VoCs in a population previously exposed to SARS-CoV-2 or after vaccination has been a challenge to understanding the kinetics of the protective immune response against this virus. The aim of this study was to investigate the outbreak of SARS-CoV-2 reinfections observed in mid-January 2022 in Rio Grande do Norte state, Brazil. It describes the clinical and genomic characteristics of nine cases of reinfection that occurred coincident with the introduction of the omicron variant. METHODOLOGY/PRINCIPAL FINDINGS: Of a total of 172,965 individuals with upper respiratory symptoms tested for SARS-CoV-2, between March 2020 through mid-February 2022, 58,097 tested positive. Of those, 444 had documented a second SARS-CoV-2 infection and nine reinfection cases were selected for sequencing. Genomic analysis revealed that virus lineages diverged between primary infections and the reinfections, with the latter caused by the Omicron (BA.1) variant among individuals fully vaccinated against SARS-CoV-2. CONCLUSIONS/SIGNIFICANCE: Our findings suggest that the Omicron variant is able to evade both natural and vaccine-induced immunity, since all nine cases had prior natural infection and, in addition, were fully vaccinated, emphasizing the need to develop effective blocking vaccines.

Differential immunoglobulin and complement levels in leprosy prior to development of reversal reaction and erythema nodosum leprosum.

BACKGROUND: Leprosy is a treatable infectious disease caused by Mycobacterium leprae. However, there is additional morbidity from leprosy-associated pathologic immune reactions, reversal reaction (RR) and erythema nodosum leprosum (ENL), which occur in 1 in 3 people with leprosy, even with effective treatment of M. leprae. There is currently no predictive marker in use to indicate which people with leprosy will develop these debilitating immune reactions. Our peripheral blood mononuclear cell (PBMC) transcriptome analysis revealed that activation of the classical complement pathway is common to both RR and ENL. Additionally, differential expression of immunoglobulin receptors and B cell receptors during RR and ENL support a role for the antibody-mediated immune response during both RR and ENL. In this study, we investigated B-cell immunophenotypes, total and M. leprae-specific antibodies, and complement levels in leprosy patients with and without RR or ENL. The objective was to determine the role of these immune mediators in pathogenesis and assess their potential as biomarkers of risk for immune reactions in people with leprosy. METHODOLOGY/FINDINGS: We followed newly diagnosed leprosy cases (n = 96) for two years for development of RR or ENL. They were compared with active RR (n = 35), active ENL (n = 29), and healthy household contacts (n = 14). People with leprosy who subsequently developed ENL had increased IgM, IgG1, and C3d-associated immune complexes with decreased complement 4 (C4) at leprosy diagnosis. People who developed RR also had decreased C4 at leprosy diagnosis. Additionally, elevated anti-M. leprae antibody levels were associated with subsequent RR or ENL. CONCLUSIONS: Differential co-receptor expression and immunoglobulin levels before and during immune reactions intimate a central role for humoral immunity in RR and ENL. Decreased C4 and elevated anti-M. leprae antibodies in people with new diagnosis of leprosy may be risk factors for subsequent development of leprosy immune reactions.

Causes of death in patients with Berardinelli-Seip congenital generalized lipodystrophy.

INTRODUCTION: Berardinelli-Seip Congenital Lipodystrophy (BSCL) is a rare autosomal recessive disease that affects the development of adipocytes and leads to an inability to store fat in adipocytes. This study aimed to evaluate the life expectancy and the causes of death of patients with BSCL. METHOD: We analyzed death certificates, and medical records of BSCL patients who died between 1997 and 2017. If the death certificate was incomplete or unavailable, we reviewed the medical records, and if they were not available too, we collected information from the patient's relatives to understand how the death happened. We calculated the potential years of life lost as a result of premature death. RESULTS: Twenty patients (12 female and 8 male) died between 1997 and 2017. The mean age at the time of death was 27.1±12.4 years (women 25.2±12.5 vs. men 29.9±12.6 years, p = 0.41). Life expectancy for the study population was 62.9±4.8 years. The potential number of years of life lost was 35.6±16.6 years. The causes of deaths were divided into three major groups: infections (7 patients, 35%), liver disease (7 patients, 35%), and other causes (acute pancreatitis, one patient; renal failure, three patients; sudden death/myocardial infarction, two patients). Three patients had pulmonary fibrosis. CONCLUSION: BSCL led to premature death, cutting the patients' lifespan by 30 or more years. The majority of these young patients died of liver disease or infection. Other studies are needed to understand better the mechanisms that predispose to infections, as well as to assess whether new therapies can alter the natural history of this disease.

Risk factors of Helicobacter pylori infection in an urban community in Northeast Brazil and the relationship between the infection and gastric diseases.

INTRODUCTION: Helicobacter pylori, a water contaminant, is the primary pathogenic agent associated with gastric diseases in humans. Exposure to H. pylori is more likely higher in developing countries. This study aimed to evaluate the risk factors associated with H. pylori infection in patients undergoing endoscopy to validate the cause of dyspeptic symptoms in an urban population in northeast Brazil and to compare the urease test and polymerase chain reaction assay results with the histopathological findings. METHODS: We evaluated 200 of 759 individuals with dyspeptic complaints from Campina Grande, State of Paraiba, northeast Brazil. Patients underwent endoscopy, followed by gastric biopsies. Logistic regression analysis was performed to adjust for confounders and to determine significant risk factors of dyspeptic disorders. RESULTS: Women accounted for 72.5% (145/200) of the participants. Approximately 59.8% (120/200) of the samples tested positive for H. pylori based on histological examinations. The specificity of polymerase chain reaction assay was higher than that of the urease test (77% vs. 64%, p=0.034). City drinking water [odds ratio (OR): 2.6; 95% confidence interval (CI): 1.3-5.21; p=0.004] and smoking (OR: 4.0; 95% CI: 1.13-14.5; p=0.031) were the risk factors of H. pylori infection. Belching was the most common symptom associated with H. pylori infection (p=0.05). CONCLUSIONS: The increased risk of H. pylori infection associated with non-treated water consumption indicates the need for improvements in public water treatment and better sanitary conditions because these can be a source of not only H. pylori infections but also other water-borne pathogen infections.

Risk factors of helicobacter pylori infection in an urban community in northeast Brazil and the relationship between the infection and gastric diseases

Abstract INTRODUCTION: Helicobacter pylori, a water contaminant, is the primary pathogenic agent associated with gastric diseases in humans. Exposure to H. pylori is more likely higher in developing countries. This study aimed to evaluate the risk factors associated with H. pylori infection in patients undergoing endoscopy to validate the cause of dyspeptic symptoms in an urban population in northeast Brazil and to compare the urease test and polymerase chain reaction assay results with the histopathological findings. METHODS: We evaluated 200 of 759 individuals with dyspeptic complaints from Campina Grande, State of Paraiba, northeast Brazil. Patients underwent endoscopy, followed by gastric biopsies. Logistic regression analysis was performed to adjust for confounders and to determine significant risk factors of dyspeptic disorders. RESULTS: Women accounted for 72.5% (145/200) of the participants. Approximately 59.8% (120/200) of the samples tested positive for H. pylori based on histological examinations. The specificity of polymerase chain reaction assay was higher than that of the urease test (77% vs. 64%, p=0.034). City drinking water [odds ratio (OR): 2.6; 95% confidence interval (CI): 1.3-5.21; p=0.004] and smoking (OR: 4.0; 95% CI: 1.13-14.5; p=0.031) were the risk factors of H. pylori infection. Belching was the most common symptom associated with H. pylori infection (p=0.05). CONCLUSIONS: The increased risk of H. pylori infection associated with non-treated water consumption indicates the need for improvements in public water treatment and better sanitary conditions because these can be a source of not only H. pylori infections but also other water-borne pathogen infections.

Bone Density in Patients With Berardinelli-Seip Congenital Lipodystrophy Is Higher in Trabecular Sites and in Type 2 Patients.

Berardinelli-Seip congenital lipodystrophy (BSCL) is a rare autosomal recessive syndrome characterized by a difficulty storing lipid in adipocytes, low body fat, hypoleptinemia, and hyperinsulinemia. We report here laboratory, bone mineral density (BMD), and bone mineral content findings of 21 patients (24.1 ± 8.4 yr old, 14 females, 18 diabetics, 5.3% total body fat) with BSCL. The mean leptin was very low (0.91 ± 0.42 ng/mL), and the mean values of the Z-scores for all studied sites were positive, except for the 33% radius (Z-score -0.5 standard deviation [SD]). Twelve patients (57.1%) had a BMD Z-score higher than +2.5 SD in at least 1 site. There was no significant difference in the Z-scores between males and females. None of type 1 (AGPAT2) patients had Z-scores higher than +2.5 SD, and these patients had a smaller Z-score of BMD total body (0.26 SD vs 1.90 SD, p = 0.022) and of bone mineral content (1.59 SD vs 3.3 SD, p = 0.032) than type 2 (seipin) patients. Insulin, as well as HOMAIR (homeostasis model assessment), correlated positively with the BMD of all sites, except for the 33% radius. Z-Scores on this site (33% radius) were the smallest of all. More than half of our patients with BSCL have BMD Z-scores higher than +2.5 SD on at least 1 site, and this increase is more pronounced in the trabecular sites and in type 2 patients.

Zinc supplementation reduces RANKL/OPG ratio and prevents bone architecture alterations in ovariectomized and type 1 diabetic rats.

Type 1 diabetes mellitus (T1DM) and estrogen deficiency are associated with several alterations in bone turnover. Zinc (Zn) is required for growth, development, and overall health. Zinc has been used in complementary therapy against bone loss in several diseases. We hypothesized that Zn supplementation represents a potential therapy against severe bone loss induced by the combined effect of estrogen deficiency and T1DM. We evaluated the protective effect of Zn against bone alterations in a chronic model of these disorders. Female Wistar rats were ramdomized into 3 groups (5 rats each): control, OVX/T1DM (ovariectomized rats with streptozotocin-induced T1DM), and OVX/T1DM+Zn (OVX/T1DM plus daily Zn supplementation). Serum biochemical, bone histomorphometric, and molecular analyses were performed. Histomorphometric parameters were similar between the control and OVX/T1DM+Zn groups, suggesting that Zn prevents bone architecture alterations. In contrast, the OVX/T1DM group showed significantly lower trabecular width and bone area as well as greater trabecular separation than the control. The OVX/T1DM and OVX/T1DM+Zn groups had significantly higher serum alkaline phosphatase activity than the control. The supplemented group had higher levels of serum-ionized calcium and phosphorus than the nonsupplemented group. The RANKL/OPG ratio was similar between the control and OVX/T1DM+Zn groups, whereas it was higher in the OVX/T1DM group. In conclusion, Zn supplementation prevents bone alteration in chronic OVX/T1DM rats, as demonstrated by the reduced RANKL/OPG ratio and preservation of bone architecture. The findings may represent a novel therapeutic approach to preventing OVX/T1DM-induced bone alterations.

Anabolic Effect of Insulin Therapy on the Bone: Osteoprotegerin and Osteocalcin Up-Regulation in Streptozotocin-Induced Diabetic Rats.

Type 1 diabetes mellitus (T1DM) is associated with several skeletal alterations, particularly in conditions of poor glycaemic control. Insulin therapy is the major conservative treatment for T1DM; however, the effects of this hormone on bone markers of T1DM rats are limited, and the regulatory mechanisms remain elusive. Therefore, the evaluation of molecular and non-molecular parameters in a chronic animal model of T1DM-induced bone loss, treated with and without insulin, may help in elucidating the insulin mechanisms. Male Wistar rats were assigned into three groups: control, T1DM (T1DM rats induced with streptozotocin [STZ] at 40 mg/kg intravenously) and T1DM plus insulin therapy (T1DMI). After 8 weeks, we evaluated the serum biochemical, tibia histomorphometric and biomechanical parameters, as well as the gene expression of the receptor activator of nuclear factor kappa-B ligand (RANKL), osteoprotegerin (OPG) and osteocalcin (OC) of femur mRNA. Compared with T1DM, the T1DMI group showed less bone loss, which was revealed by the increased trabecular width (TbWi, p < 0.001) and trabecular bone area (BAr, p < 0.01), reduced trabecular separation (TbSp, p < 0.01) and increased Young's modulus (p < 0.05). Moreover, molecular analyses indicated that the expression of OPG and OC was up-regulated (p < 0.001 and p < 0.05, respectively). In summary, the up-regulation of OPG and OC in the T1DMI group supports an anabolic effect of insulin, which was demonstrated by the maintenance of bone architecture and flexibility. These results suggest that insulin therapy may prevent T1DM-induced bone loss via the effects on the bone formation.

Zinc supplementation reduces RANKL/OPG ratio and prevents bone architecture alterations in ovariectomized and type 1 diabetic rats

Type 1 diabetes mellitus (T1DM) and estrogen deficiency are associated with several alterations in bone turnover. Zinc (Zn) is required for growth, development, and overall health. Zinc has been used in complementary therapy against bone loss in several diseases. We hypothesized that Zn supplementation represents a potential therapy against severe bone loss induced by the combined effect of estrogen deficiency and T1DM. We evaluated the protective effect of Zn against bone alterations in a chronic model of these disorders. Female Wistar rats were ramdomized into 3 groups (5 rats each): control, OVX/T1DM (ovariectomized rats with streptozotocin-induced T1DM), and OVX/T1DM+Zn (OVX/T1DM plus daily Zn supplementation). Serum biochemical, bone histomorphometric, and molecular analyses were performed. Histomorphometric parameters were similar between the control and OVX/T1DM+Zn groups, suggesting that Zn prevents bone architecture alterations. In contrast, the OVX/T1DM group showed significantly lower trabecular width and bone area as well as greater trabecular separation than the control...

No association between FCGR2A and FCGR3A polymorphisms in Guillain-Barré Syndrome in a Brazilian population.

The pathogenesis of Guillain-Barré Syndrome (GBS) is not entirely understood, but includes infection-induced aberrant immune responses. Genetic polymorphisms in Fc gamma receptor genes (FCGR) have been associated with GBS. We assessed whether polymorphisms rs1801274 in FCGR2A and rs396991 in FCGR3A were associated with GBS in a Brazilian population. We genotyped 141 GBS cases and 364 healthy controls from Brazil for both polymorphisms. The FCGR genotypes and alleles frequencies did not differ significantly between GBS and controls. In addition, there was no genetic association with either severity or clinical outcomes. We conclude that these FCGR polymorphisms are not associated with susceptibility to Guillain-Barré Syndrome in this Brazilian population.

Association of polymorphisms in IL6 gene promoter region with type 1 diabetes and increased albumin-to-creatinine ratio.

BACKGROUND: Pro-inflammatory cytokines, such as interleukin-6 (IL-6), have been considered as key factors in type 1 diabetes mellitus (T1DM) and diabetic nephropathy, thus, our aim was to investigate the association of IL6-174G>C (rs1800795) and -634C>G (rs1800796) polymorphisms with T1DM susceptibility and diabetic nephropathy. METHODS: These polymorphisms were analyzed in 144 children and adolescents with T1DM and 173 normoglycemic control subjects. Glycemic control, laboratory parameters of kidney function and serum lipids were evaluated. By studying only T1DM patients, we evaluated the polymorphisms associated with relevant biochemical parameters in various genetic models. RESULTS: Type 1 diabetes mellitus patients showed poor glycemic control and albumin-to-creatinine ratio, total cholesterol and LDL-cholesterol levels increased when compared with normoglycemic subjects (p < 0.001, p = 0.004 and p < 0.001, respectively). IL6-174C allele was associated with an increased risk of developing T1DM (OR = 1.53, CI = 1.01-2.31, p = 0.044). In the T1DM group, IL6-174CC carriers showed higher concentrations of glycated hemoglobin (p = 0.029), albumin-to-creatinine ratio (p = 0.021), total cholesterol (p = 0.010), and LDL-cholesterol (p = 0.002), when compared with GG+GC carriers. No association was found for the IL6-634C>G polymorphism. CONCLUSIONS: These results suggest that IL6-174G>C may contribute to T1DM and increased albumin-to-creatinine ratio as well as to poor glycemic control and hyperlipidemia.

Dual immune modulatory effect of vitamin A in human visceral leishmaniasis.

Vitamin A supplementation has shown to prevent mortality by diarrheal and respiratory diseases in several countries. Nevertheless, there are few studies investigating the effect of vitamin A in visceral leishmaniasis (VL), although there are reports of its deficiency in children with symptomatic VL in Brazil and Bangladesh. This study analyzed the effect of vitamin A on a subset of Treg cells and monocytes isolated from symptomatic VL and from healthy children residing in an endemic area for VL in Northeast Brazil. Serum retinol concentrations correlated inversely with IL-10 and TGF-ß productions in CD4(+)CD25(high)Foxp3(+) T cells isolated from children with VL stimulated with leishmanial antigens. All-trans retinoic acid in vitro induced IL-10 in CD4(+)CD25(high)Foxp3(+) T cells; IL-10 and TGF-ß production in CD4(+)CD25-Foxp3- T cells, and IL-10 in monocytes isolated from healthy children. However, the use of all-trans retinoic acid together with leishmanial antigens in vitro prevented increases in IL-10 production in Treg cells and monocytes isolated from VL children. Strikingly, those results show a potential dual role of vitamin A in the immune system: improvement of a regulatory profile in cells from healthy children after leishmanial stimulation and down modulation of IL-10 in Treg cells and monocytes during symptomatic VL. Therefore, the use of vitamin A concomitant to VL therapy might be useful in improving recovery from disease status caused by Leishmania infantum infection and warrants additional study.

Low bone mineral density is associated to poor glycemic control and increased OPG expression in children and adolescents with type 1 diabetes.

AIMS: To investigate early alterations on bone mineral density (BMD) and RANK, RANKL and OPG mRNA expression in peripheral blood leukocytes (PBL) in children and adolescents with type 1 diabetes (T1D) and the relationship with glycemic control and bone biomarkers. METHODS: This cross-sectional study included 75 children and adolescents with T1D and 100 individuals without diabetes (normoglycemic-NG) aged 6-20 years old. T1D individuals were considered to have good (T1DG) or poor (T1DP) glycemic control according to the values of HbA1c. Phosphorus, magnesium, total and ionized calcium, osteocalcin, alkaline phosphatase and tartaric-resistant acid phosphatase (TRAP) values were determined in blood samples. BMD was measured by DEXA. RANK, RANKL and OPG mRNA expression was measured in PBL by real-time PCR. RESULTS: Osteocalcin values were decreased in diabetic groups in comparison to NG group (p<0.05), and a negative correlation with both serum glucose (r=-0.265, p<0.01) and Hb1Ac (r=-0.252, p<0.01) in T1D group was found. BMD was lower in diabetic groups in comparison with NG group (p<0.05) and a negative correlation was observed between BMD and both serum glucose (r=-0.357, p<0.01) and HbA1c (r=-0.351, p<0.01) in T1D group. OPG mRNA expression was significantly increased in T1D and T1DP groups in comparison with NG group (p<0.05). In conclusion, children and adolescents with early onset T1D presented low bone mineral density associated to unsatisfactory glycemic control, increased OPG mRNA expression and low osteocalcin concentration.

Association of pro-inflammatory cytokines and iron regulatory protein 2 (IRP2) with Leishmania burden in canine visceral leishmaniasis.

Leishmania infantum infection in humans and dogs can evolve with a wide range of clinical presentations, varying from asymptomatic infections to visceral leishmaniasis. We hypothesized that the immune response elicited by L. infantum infection could modulate whether the host will remain asymptomatic or progress to disease. A total of 44 dogs naturally infected with L. infantum were studied. Leishmania burden was estimated in the blood and spleen by qPCR. The expression of IFN-γ, TNF-α, IL-10 and Iron Regulatory Protein 2 (IRP2) were determined in the spleen by quantitative PCR. Sera cytokines were evaluated by ELISA. Dogs were grouped in quartiles according parasite burden. Increased expression of IFN-γ and TNF-α was associated with reduced Leishmania burden, whereas increased IL-10 and IRP2 expressions were associated with higher Leishmania load. Increased plasma albumin and IFN-γ expression explained 22.8% of the decrease in parasite burden in the spleen. These data confirm that lower IFN-γ response and higher IL-10 correlated with increased parasite load and severity of the visceral leishmaniasis in dogs. The balance between the branches of immune response and the intracellular iron availability could determine, in part, the course of Leishmania infection.

Oophorectomy hinders antioxidant adaptation promoted by swimming in Wistar rats.

Oxidative stress is associated with postmenopause and is also responsible for various metabolic alterations. The redox imbalance observed during ovarian decline can be induced experimentally by bilateral ovariectomy in rats. In addition to hormone replacement, regular moderate physical exercise is indicated to prevent several common postmenopausal diseases. This study aimed to assess the effect of daily swimming on the antioxidant defense system of oophorectomized Wistar rats. Control and oophorectomized groups were submitted to 1 h of daily swimming for 90 days. Levels of lipid peroxidation and glutathione content and the activities of superoxide dismutase enzyme and glutathione peroxidase in erythrocytes, liver, and brain were assessed every 30 days. The control group exhibited lower lipoperoxidation that was associated with a significant increase in superoxide dismutase enzyme activity, glutathione peroxidase activity, and glutathione content in erythrocytes and liver; however, swimming did not cause changes in antioxidant parameters in the brain over time. The oophorectomized group showed no antioxidant adaptation to daily swimming and had greater oxidative damage in the liver and blood. Our results suggest that ovariectomy hinders antioxidant adaptation in Wistar rats submitted to daily swimming.

Increased TLR2 expression in patients with type 1 diabetes: evidenced risk of microalbuminuria.

OBJECTIVE: To study the activation of an inflammatory cascade through leukocyte mRNA expression of TLR2, TLR4, MyD88, and pro-inflammatory cytokines in individuals with childhood onset type 1 diabetes. DESIGN AND METHODS: Seventy-six type 1 diabetic patients and 100 normoglycemic subjects (NG) 6 to 20 years old were recruited. Type 1 diabetic patients (DM1) were considered to have good (DM1G) or poor (DM1P) glycemic control according to the values of glycated hemoglobin. TLR2, TLR4, MyD88, interleukin -1ß (IL-1ß), IL-6, and tumor necrosis factor alpha (TNF-α) mRNA expressions were measured in peripheral blood leukocytes (PBL) by real-time polymerase chain reaction (PCR). Urea, creatinine, albumin, and total protein serum levels were determined. Urinary albumin-to-creatinine ratio (ACR) was calculated. RESULTS: DM1 and DM1P patients showed higher glycated hemoglobin (10 and 11%, respectively) and serum glucose concentrations (208 and 226 mg/dL, respectively) compared to NG (Glycated hemoglobin: 7% and glucose: 76 mg/dL) (p < 0.05). PBL mRNA expressions of TLR2, MyD88, IL-1ß, IL-6, and TNF-α were higher in DM1 and TLR2, IL-1ß, and IL-6 expressions were higher in DMP1 compared to NG (p < 0.05). In DM1, serum albumin and total protein were lower, while serum urea and ACR were higher in comparison to NG (p < 0.05). However, these differences compared to NG were more pronounced in DM1P, which included nine individuals with microalbuminuria. CONCLUSIONS: Increased mRNA expression of TLR2, MyD88, and pro-inflammatory cytokines in leukocytes of patients with childhood onset type 1 diabetes indicates the development of a TLR2-mediated pro-inflammatory process, which may also be associated with an early inflammatory process in the kidney and the occurrence of microalbuminuria.

Relationship between oxidative stress and diabetic osteopenia in premenopausal rats / Relação entre o estresse oxidativo ea osteopenia diabética em ratos pré-menopausa

The relationship between lipid peroxidation, antioxidant defense and diabetic osteopenia remains unclear. This study evaluated the relationship among lipid peroxidation index, antioxidant defense parameters and bone metabolism in a premenopausal diabetic model using measures including thiobarbituric acid-reactive substances concentration (TBARS) and reduced glutathione (GSH) content in brain homogenates, histomorphometric analysis, biomechanical testing and bone mineral density (BMD). Female Wistar rats with regular estrous cycle were divided into two groups: Group 1: control rats (n = 15) and Group 2: diabetic rats (n = 15). Diabetes was induced by alloxan and confirmed by glycemia >250 mg/dL. The lipid peroxidation index, measured by TBARS concentration, showed a significant increase (p<0.05) in diabetic animals in comparison to control animals. However, the antioxidant parameter measured by GSH content, was significantly lower (p<0.05) in diabetic animals. Histomorphometric analysis showed a significant increase (p<0.05) in femoral trabecular separation together with a significant decrease (p<0.05) in trabecular thickness, and reduced trabecular bone volume in diabetic rats. Moreover, biomechanical testing and BMD values were significantly lower (p<0.05) in the diabetic group. Thus, our results demonstrated that increased lipid peroxidation and altered antioxidant defense could be related to the development of oxidative stress and diabetic osteopenia in premenopausal rats.

A relação entre peroxidação lipídica, defesa antioxidante e osteopenia diabética permanece obscura. Este estudo avaliou a associação entre índice de peroxidação lipídica, parâmetro de defesa antioxidante e metabolismo ósseo em um modelo diabético pré-menopausa através de medidas como a concentração de substâncias reativas ao ácido tiobarbitúrico (SRAT) e conteúdo de glutationa reduzida (GSH) no homogenato cerebral, análises histomorfométricas, teste biomecânico e densidade mineral óssea (DMO). Ratos Wistar fêmeas com ciclo estral regular foram distribuídos em dois grupos: Grupo 1 - ratas controle (n = 15) e Grupo 2 - ratas diabéticas (n = 15). O diabetes foi induzido pela aloxana e confirmado pela glicemia >250 mg/dL. O índice de peroxidação lipídica, medido pela concentração de SRAT, demonstrou um aumento significativo (p<0.05) nos animais diabéticos, em relação aos animais controle. Entretanto, o parâmetro de defesa antioxidante, mensurado pelo conteúdo de GSH, foi reduzido significativamente (p<0.05) nos animais diabéticos. As análises histomorfométricas mostraram um aumento significativo (p<0.05) da separação trabecular do fêmur, associado à diminuição significativa da espessura trabecular (p<0.05) e volume ósseo trabecular reduzido nas ratas diabéticas. Além disso, o teste biomecânico, medido pela força máxima, e valores de DMO foram reduzidos significativamente (p<0.05) no grupo diabético. Dessa maneira, nossos resultados demonstraram que a peroxidação lipídica aumentada e defesa antioxidante modificada podem estar relacionadas ao desenvolvimento do estresse oxidativo e osteopenia diabética em ratas pré-menopausadas.

Liver iron overload induced by tamoxifen in diabetic and non-diabetic female Wistar rats.

Tamoxifen (TX), a drug used in the treatment of breast cancer, may cause hepatic changes in some patients. The consequences of its use on the liver tissues of rats with or without diabetes mellitus (DM) have not been fully explored. The purpose of this study was to evaluate the correlation between plasma hepatic enzyme levels and the presence of iron overload in the hepatic tissue of female Wistar rats with or without streptozotocin-induced DM and using TX. Female rats were studied in control groups: C-0 (non-drug users), C-V (sorbitol vehicle only) and C-TX (using TX). DM (diabetic non-drug users) and DM-TX (diabetics using TX) were the test groups. Sixty days after induced DM, blood samples were collected for glucose, alanine aminotransferase (ALT), aspartate aminotransferase (AST) alkaline phosphatase (ALP) and bilirubin measures. Hepatic fragments were processed and stained with hematoxylin and eosin, Masson's trichrome, Perls. The hepatic iron content was quantified by atomic absorption spectrometry. AST, ALT and ALP levels were significantly elevated in the DM and DM-TX groups, with unchanged bilirubin levels. Liver iron overload using Perls stain and atomic absorption spectrometry were observed exclusively in groups C-TX and DM-TX. There was positive correlation between AST, ALT and ALP levels and microscopic hepatic siderosis intensity in group DM-TX. In conclusion, TX administration is associated with liver siderosis in diabetic and non-diabetic rats. In addition, TX induced liver iron overload with unaltered hepatic function in non-diabetic rats and may be a useful tool for investigating the biological control of iron metabolism.