Insulin Resistance and Its Association With Osteoporosis in People Living With HIV.

Background: Despite the gain in life expectancy that people living with HIV (PLHIV) have had in the past few years, the disease is accompanied by an increase in the prevalence of noninfectious chronic diseases. PLHIV have a higher prevalence of osteoporosis, fracture, diabetes mellitus, and insulin resistance than the general population. It is unknown if insulin resistance is associated with osteoporosis and fractures in PLHIV. Our study aimed to assess the association between insulin resistance and osteoporosis in PLHIV. Methods: A cross-sectional study was carried out in southern Brazil. PLHIV ages 50 years or older on antiretroviral treatment were included. Insulin resistance was considered present when the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) was higher than expected for the Brazilian population (>2.7). The triglyceride-glucose (TyG) index was also calculated. Results: Of the 101 PLHIV who agreed to participate, 84 underwent insulin and bone mineral density measurements. The prevalence of osteoporosis was 19%. The frequency of insulin resistance calculated by HOMA-IR was 68.2%. Participants with osteoporosis had lower body mass index (BMI) and triglyceride values than those without it. HOMA-IR [4.8(6.6) vs 8.68(9.6), P = 0.013] and TyG [5.0(0.3) vs 5.2 (0.4), P = 0.029]. The association between the total femur t-score disappeared after correction for BMI in the linear regression model. There was no association between vertebral fractures and insulin resistance. Conclusion: In our study, PLHIV with osteoporosis have lower insulin resistance than PLHIV without it. However, this finding appears to be related to lower BMI. The association between insulin resistance and bone in PLHIV appears to be somewhat similar to that of the general population.

Effects of Freeze-Thaw Cycles and Assessment of Short-Term Storage Stability on Serum Iron, Ferritin, and Transferrin.

BACKGROUND: Most errors in the laboratory occur due to processes related to the pre-analytical phase. The purpose of this study was to investigate the effects of multiple freeze-thaw cycles on serum iron, transferrin, and ferritin, as well as the impact of short-term storage on the stability of these analytes. METHODS: Serum samples from ten volunteers were submitted to three consecutive freeze-thaw cycles at -20°C and -80°C. Serum aliquots were also kept at 4°C, -20°C, and -80°C for 28 days. Iron, ferritin, and transferrin were measured after 1, 7, 14, 21, or 28 days of storage. RESULTS: Serum ferritin and transferrin showed variations from -2.6 to 2.6% and -1.7 to 2.4%, respectively, in their concentrations during the three freeze-thaw cycles of -20°C and -80°C. However, the variations were statistically significant only at -20°C. No significant changes were found for iron at both temperatures. The storage at temperatures of 4°C, -20°C, and -80°C for up to 4 weeks significantly affected the serum concentrations of iron, ferritin, and transferrin (p < 0.01 for all). CONCLUSIONS: Serum iron, ferritin, and transferrin were affected by the storage of samples at temperatures of 4°C, -20°C and -80°C for up to 4 weeks, and the freeze-thaw cycles at -20°C influenced the measurement of serum ferritin and transferrin.

Sarcopenia and Its Association with Vertebral Fractures in People Living with HIV.

The prevalence of chronic diseases is increasing in people living with HIV (PLHIV) in the post ART era. Sarcopenia is prevalent in the elderly and is associated with many chronic diseases. Our study aimed to evaluate the frequency of sarcopenia in PLHIV and its association with bone mineral density and fracture. A cross-sectional study was carried out at Santa Maria, South Brazil. It included PLHV age ≥ 50 years and registered to receive antiretroviral therapy. A structured questionnaire was applied, blood samples collected, muscle strength evaluated, body composition measured, and vertebral morphometry performed. Sarcopenia and presarcopenia were defined according to the European Working Group on Sarcopenia in Older People. Of the 101 patients recruited, 83 underwent DXA and muscle strength measurements. The prevalence of sarcopenia and presarcopenia in the individuals studied was 12% and 16.9%, respectively. 66.7% of sarcopenic individuals had morphometric vertebral fractures and there was a tendency towards a higher frequency of multiple vertebral fractures when compared with non-sarcopenic subjects (44.4% vs. 16.2%, p = 0.066). BMI and total hip BMD were significantly lower in sarcopenic than non-sarcopenic individuals (p ≥ 0.035 and 0.032 respectively). In multiple regression analysis, sarcopenia was associated with age and multiple vertebral fractures. Sarcopenia was present in 12% of this population of PLHIV age ≥ 50 years and was associated with lower hip BMD and a high prevalence of vertebral fractures.

Low frataxin mRNA expression is associated with inflammation and oxidative stress in patients with type 2 diabetes.

BACKGROUND: The mitochondrial protein frataxin is involved in iron metabolism, as well as regulation of oxidative stress. To elucidate the association of frataxin with the pathophysiology of diabetes, we evaluated the mRNA levels of frataxin in leukocytes of patients with type 2 diabetes (T2D). In addition, we investigated the relation between frataxin mRNA levels, inflammatory cytokines, and oxidative stress biomarkers. METHODS: A study including 150 subjects (115 patients with T2D and 35 healthy subjects) was performed to evaluate the frataxin mRNA levels in leukocytes. We assessed the relation between frataxin and interleukin (IL)-6, IL-1, tumour necrosis factor-alpha (TNF-α), total oxidation status (TOS), total antioxidant capacity (TAC), and serum iron. RESULTS: The frataxin mRNA levels in the T2D group were significantly lower than those in healthy subjects. It was also demonstrated that T2D patients with frataxin mRNA levels in the lowest quartile had significantly elevated levels of serum iron, TOS, and inflammatory cytokines, such as TNF-α, IL-1, and IL-6, while TAC levels were significantly lower in this quartile when compared with the upper quartile. CONCLUSIONS: Our findings showed that T2D patients with low frataxin mRNA levels showed a high degree of inflammation and oxidative stress. It is speculated that frataxin deficiency in T2D patients can contribute to the imbalance in mitochondrial iron homeostasis leading to the acceleration of oxidative stress and inflammation.

Association between Urinary Levels of Interleukin-6, Interleukin-10 and Tumor Necrosis Factor-Alpha with Glomerular and Tubular Damage Indicators in Patients with Type 2 Diabetes.

BACKGROUND: This study investigated the association between urinary levels of interleukin (IL)-6, IL-10, and tumor necrosis factor-alpha (TNF-α) with estimated glomerular filtration rate (eGFR), urinary albumin/creatinine ratio (uACR), and urinary neutrophil gelatinase-associated lipocalin (uNGAL) in patients with type 2 diabetes (T2D). METHODS: Urinary concentrations of IL-6, IL-10, TNF-α, ACR, and NGAL were measured in 121 patients with T2D. RESULTS: Urinary IL-6 and TNF-α increased 45.5% and 49.4% in the highest uACR quartile compared to lowest quartile. Urinary IL-10 levels decreased 40.9% in the highest uACR quartile compared to the lowest quartile. Urinary IL-6 and TNF-α were 75.3% and 81.6%, higher in the highest uNGAL quartile compared to the lowest quartile. Urinary IL-10 concentration was 69.8% lower in patients from the highest uNGAL quartile compared to lowest quartile. CONCLUSIONS: Urinary IL-6, IL-10, and TNF-α were associated with indicators of glomerular and tubular injuries in patients with T2D.

High Serum Uric Acid Is Associated with Tubular Damage and Kidney Inflammation in Patients with Type 2 Diabetes.

BACKGROUND: Uric acid presents different roles in an organism. High serum uric acid concentrations may induce inflammatory pathways and promote kidney damage through different mechanisms. Therefore, this study investigated the association among high serum uric acid concentrations, renal tubular damage, and renal inflammation assessed via estimation of urinary kidney injury molecule-1 (KIM-1) and inflammatory cytokines in patients with type 2 diabetes (T2D). METHODS: Urinary concentrations of KIM-1, IL-1, IL-6, IL-10, and TNF-alpha, as well as other biochemical parameters, were assessed in 125 patients with T2D who were grouped into two groups based on the serum uric acid levels (<6.0 mg/dL and ≥6.0 mg/dL). Patients were also stratified according to the tertiles of serum uric acid concentrations. RESULTS: Urinary KIM-1, IL-1, IL-6, and TNF-alpha were higher in patients with serum uric acid concentrations ≥ 6.0 mg/dL. However, the differences between the groups were not statistically significant when the urinary values of KIM-1 and cytokines were normalized by the urinary creatinine concentration. Serum uric acid concentrations were significantly associated with urinary KIM-1 (values normalized by urinary creatinine concentration) and urinary TNF-alpha (absolute values and values normalized by urinary creatinine concentration), independent of the body mass index (BMI) and estimated glomerular filtration rate (eGFR). CONCLUSIONS: High serum uric acid concentrations were associated with high urinary KIM-1 levels accompanied by the increase of urinary proinflammatory cytokines in patients with T2D. However, normalization of urinary markers by urine creatinine concentration seems to influence the profile of the results.

Nanoencapsulation of the flavonoid dihydromyricetin protects against the genotoxicity and cytotoxicity induced by cationic nanocapsules.

We evaluated the influence of nanoencapsulation of the flavonoid Dihydromyricetin (DMY) in reducing the genotoxicity and cytotoxicity induced by cationic nanocapsules. Assays were conducted in order to evaluate the potential of protein corona formation, cytotoxicity, genotoxicity and the antioxidant capacity. Nanocapsules containing DMY (NC-DMY) and free DMY (DMY-F) did not demonstrate cytotoxicity and genotoxicity. However, Eudragit RS100® nanocapsules (NC-E) increased cytotoxicity and DNA damage formation. NC-DMY and NC-E presented high interaction with the DNA in vitro, suggesting DNA sequestration. These results indicate that nanoencapsulated DMY does not induce cytotoxicity or genotoxicity, and demonstrates high antioxidant capacity. This antioxidant capacity is probably associated with DMY, and occurs due to its ability to avoid the formation of free radicals, thus preventing the toxicity caused by the nanostructure with the cationic polymer Eudragit RS100®. Therefore, NC-DMY can be considered an important formulation with significant antioxidant potential to be exploited by nanomedicine.

Acetylcholinesterase activity and total antioxidant levels in dogs with mammary tumors before and after surgical removal / Actividad de acetilcolinesterasa y niveles totales de antioxidantes en perros con tumores de mama antes y después de la extirpación quirúrgica

ABSTRACT Objective. The aim of this study was to evaluate AChE activity in total blood and the FRAP levels in samples from dogs with mammary tumors before and after surgery, as well as the relationship between these variables with immunohistochemical markers of tumor (E-caderina, ki-67, COX-2). Materials and methods. In this study, 13 dogs with mammary tumors were divided into two groups (A and B). The group A was formed by dogs with tumors smaller than 3 cm of diameter, and the group B was formed by dogs with tumor of 3 cm of diameter or larger. The AChE activity and FRAP levels were evaluated before and after surgery and the immunohistochemistry were performed at the tumors. Results. The AChE activity was significantly increased (p<0.05) in dogs with mammary cancer compared to control animals, and neither surgery or tumor size affected the AChE activity (p>0.05). FRAP levels before surgery were significantly lower (p<0.05) compared to control animals. Also, FRAP levels increased significantly after surgery in animals of the group A compared to data before surgery, a fact not observed in dogs from the group B. E-cadherin showed low significant positive correlation with FRAP levels (r=0.37, p-value=0.05); COX-2 showed a moderate significant positive correlation to FRAP (r=0.55, p-value<0.05); and COX-2 showed a low significant positive correlation to AChE (r=0.32, p-value=0.01). Conclusions. AChE and antioxidant levels are modified in dogs with mammary cancer. These variables are involved in various physiological functions, and thus, they might be related to disease pathogenesis.

RESUMEN Objetivo. Evaluar la actividad de la AChE en sangre total y los niveles de FRAP en muestras de perros con tumores mamarios antes y después de la cirugía, así como la relación entre estas variables con marcadores inmunohistoquímicos de tumores (E-caderina, ki-67 , COX - 2). Materiales y métodos. En este estudio, 13 perros con tumores mamarios se dividieron en dos grupos (A y B). El grupo A estaba formado por perros con tumores menores de 3 cm de diámetro y el grupo B estaba formado por perros con tumor de 3 cm de diámetro o más. La actividad de AChE y los niveles de FRAP se evaluaron antes y después de la cirugía y la inmunohistoquímica se realizó en los tumores. Resultados. La actividad de la AChE aumentó significativamente (p<0.05) en perros con cáncer mamario en comparación con los animales control, y ni la cirugía ni el tamaño tumoral afectaron la actividad de la AChE (p>0.05). Los niveles de FRAP antes de la cirugía fueron significativamente más bajos (p<0.05) en comparación con los animales control. Además, los niveles de FRAP aumentaron significativamente después de la cirugía en animales del grupo A en comparación con los datos antes de la cirugía, hecho que no se observó en perros del grupo B. La E-cadherina mostró correlación positiva baja con los niveles de FRAP (r = 0.37, valor p=0.05); COX-2 mostró una moderada correlación positiva significativa con FRAP (r = 0.55, p-valor<0.05); Y la COX-2 mostró una correlación positiva de baja significación con la AChE (r = 0.32, p-valor = 0.01). Conclusiones. AChE y los niveles de antioxidantes se modifican en perros con cáncer de mama. Estas variables están implicadas en diversas funciones fisiológicas, y por lo tanto, pueden estar relacionadas con la patogénesis de la enfermedad.

High serum uric acid is associated with oxidation of nucleosides in patients with type 2 diabetes.

Uric acid presents different roles in an organism, since it can act as an antioxidant or a pro-oxidant molecule. High serum uric acid levels may cause damage to several structures, including nucleic acids and its components. Therefore, in this study the association between increased serum uric acid concentrations and oxidation of nucleosides was investigated by assessment of urinary 8-hydroxydeoxyguanosine (8-OHdG) in patients with type 2 diabetes (T2D) and in healthy individuals. Urinary 8-OHdG and biochemical parameters were assessed in 61 patients who were initially grouped into 2 groups based on the median serum uric acid levels (<5.3 mg/dL and ≥5.3 mg/dL). Urinary 8-OHdG was higher in patients with T2D and serum uric acid levels ≥5.3 mg/dL, when compared with the patients with serum uric acid levels <5.3 mg/dL; however, co-occurrence of high serum uric acid with high urinary 8-OHdG was not observed in healthy individuals. A significant positive correlation between 8-OHdG and uric acid (r = 0.40, P < 0.01) was observed in patients with T2D. High serum uric acid levels were associated with high urinary 8-OHdG levels in patients with T2D, and this association was independent of gender, hypertension, body mass index, and serum creatinine.

Urinary kidney injury molecule-1 in renal disease.

Kidney injury molecule-1 (KIM-1), a type l transmembrane glycoprotein, is recognized as a potential biomarker for detection of tubular injury in the main renal diseases. Urinary KIM-1 increases rapidly upon the tubular injury, and its levels are associated with the degree of tubular injury, interstitial fibrosis, and inflammation in the injured kidney. Currently, the investigation of kidney diseases is usually performed through the assessment of serum creatinine and urinary albumin. However, these biomarkers are limited for the early detection of changes in renal function. Besides, the tubular injury appears to precede glomerular damage in the pathophysiology of renal diseases. For these reasons, the search for sensitive, specific and non-invasive biomarkers is of interest. Therefore, the purpose of this article is to review the physiological mechanisms of KIM-1, as well to present clinical evidence about the association between elevated urinary KIM-1 levels and the main renal diseases such as chronic kidney disease, diabetic kidney disease, acute kidney injury, and IgA nephropathy.