Intravenous Vitamin C as an Add-on Therapy for the Treatment of Sepsis in an Intensive Care Unit: A Prospective Cohort Study.

Background and Objectives: According to the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3), sepsis is defined as "life-threatening organ dysfunction caused by a dysregulated host response to infection". The increased presence of free radicals causes an increase in oxidative stress. Vitamin C is an essential water-soluble vitamin with antioxidant activity and immunoregulatory effects that plays a potential role in the treatment of bacterial infections. Our aim was to evaluate the effectiveness of adding vitamin C to the conventional treatment of sepsis to decrease its mortality rate. Materials and Methods: In a prospective cohort study, we included patients with a diagnosis of sepsis and a SOFA score ≥ 9 who were evaluated in an Intensive Care Unit at a secondary-care hospital. According to the intensive care specialist, they were treated using two different strategies: Group 1-patients with sepsis treated with conventional treatment without vitamin C; Group 2-patients with sepsis with the addition of vitamin C to conventional treatment. Results: We included 34 patients with sepsis. The incidence of mortality was 38%, and 47% of patients used vitamin C as an adjuvant to the basic treatment of sepsis. In the basal analyses, patients treated with use of vitamin C compared to patients treated without vitamin C required less use of glucocorticoids (75% vs. 100%, p = 0.039). At follow-up, patients treated without vitamin C had higher mortality than patients treated with vitamin C as an adjuvant for the treatment of sepsis (55.6% vs. 18.8%, p = 0.03). We observed that the use of vitamin C was a protective factor for mortality in patients with sepsis (RR: 0.54, 95% CI: 0.31-0.96, p = 0.03). Conclusions: The use of vitamin C as an adjuvant to treatment decreases the risk of mortality by 46% in patients with sepsis and SOFA ≥ 9 compared to patients treated without vitamin C as an adjuvant to sepsis.

Therapeutic Targets for Regulating Oxidative Damage Induced by Ischemia-Reperfusion Injury: A Study from a Pharmacological Perspective.

Ischemia-reperfusion (I-R) injury is damage caused by restoring blood flow into ischemic tissues or organs. This complex and characteristic lesion accelerates cell death induced by signaling pathways such as apoptosis, necrosis, and even ferroptosis. In addition to the direct association between I-R and the release of reactive oxygen species and reactive nitrogen species, it is involved in developing mitochondrial oxidative damage. Thus, its mechanism plays a critical role via reactive species scavenging, calcium overload modulation, electron transport chain blocking, mitochondrial permeability transition pore activation, or noncoding RNA transcription. Other receptors and molecules reduce tissue and organ damage caused by this pathology and other related diseases. These molecular targets have been gradually discovered and have essential roles in I-R resolution. Therefore, the current study is aimed at highlighting the importance of these discoveries. In this review, we inquire about the oxidative damage receptors that are relevant to reducing the damage induced by oxidative stress associated with I-R. Several complications on surgical techniques and pathology interventions do not mitigate the damage caused by I-R. Nevertheless, these therapies developed using alternative targets could work as coadjuvants in tissue transplants or I-R-related pathologies.

Serum irisin concentrations and osteoporotic vertebral fractures in women with rheumatoid arthritis: A cross-sectional study.

ABSTRACT: Irisin stimulates osteoblast differentiation increasing bone mass a decreasing in irisin levels might contribute to osteoporotic fractures in inflammatory diseases. To date, there is controverted whether irisin levels are associated with osteoporotic fractures in rheumatoid arthritis (RA). Therefore, we evaluate the association of serum irisin with osteoporotic Vertebral Fractures (VFs) in women with RA.A total of 148 women with RA was included in the study.Clinical characteristics and risk factors of VFs was evaluated. For measurement of bone mineral density we included the assessment of lumbar spine (AP L1-L4) and Femoral Neck by dual-energy X-ray absorptiometry (DXA). VFs were evaluated by lateral vertebral assessment (LVA) of the dorsal and lumbar regions using X-ray and digital vertebral morphometry by DXA, using the Genant scale. Serum irisin levels were measured by ELISA. A reference group of 97 women with non-rheumatic diseases were included to compare irisin levels.RA patients had a median age of 59 years and 41% had osteoporosis. Seventy three (49%) had VFs. Lower irisin levels were observed in RA patients compared to controls (94 ±â€Š74 vs 135 ±â€Š103, P < .001). Irisin concentrations were lower in RA + VFs than RA non-VFs (74 ±â€Š42 vs 113 ±â€Š92 ng/mL, P = .001). In the multivariable logistic regression analysis the low 50 percentile irisin levels < 73 ng/mL (OR:3.1, 95% CI:1.55-6.2, P = .001), and disease duration of RA (OR:1.04, 95% CI:1.001-1.08, P = .04) were associated with an increase in the risk of VFs.A decrease of irisin levels is associated to VFs in RA. These results are valuable to consider that RA patients with low levels of irisin are in a potential risk of VFs.

Effect of Telmisartan in the Oxidative Stress Components Induced by Ischemia Reperfusion in Rats.

The therapeutic effects of telmisartan, an angiotensin II receptor antagonist and a peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist, have been demonstrated in several disorders. It has antioxidant and immune response modulator properties and has shown promising results in the treatment of an ischemia/reperfusion (I/R) lesion. In this study, a skeletal muscle (right gastrocnemius muscle) I/R lesion was induced in rats and different reperfusion times (1 h, 24 h, 72 h, 7-day, and 14-day subgroups) were assessed. Furthermore, levels of oxidative markers such as enzymatic scavengers (catalase (CAT) and superoxide dismutase (SOD)) and metabolites (nitrates and 8-oxo-deoxyguanosine) were determined. The degree of tissue injury (total lesioned fibers and inflammatory cell count) was also evaluated. We observed an increase in CAT and SOD expression levels under telmisartan treatment, with a decrease in injury and oxidative biomarker levels in the 72 h, 7-day, and 14-day subgroups. Telmisartan reduced oxidative stress and decreased the damage of the I/R lesion.

Efficacy and safety of the combination of isosorbide dinitrate spray and chitosan gel for the treatment of diabetic foot ulcers: A double-blind, randomized, clinical trial.

AIM: To evaluate whether a combination of isosorbide dinitrate spray and chitosan gel (10%) topically applied can have additive benefits for management of diabetic foot ulcers. METHODS: In a randomized, placebo-controlled, double-blinded clinical trial, 68 patients were divided into four groups: Group 1: treated with chitosan gel; Group 2: isosorbide dinitrate spray; Group 3: combination of isosorbide dinitrate spray and chitosan gel; Group 4: placebo. RESULTS: Histological analyses showed a significant regeneration in all groups ( p < 0.001). On the final assessment of the ulcer, using the combination was found a wound closure percentage of 71 ± 30, 70 ± 27 using isosorbide dinitrate, 58 ± 30 with chitosan and 50 ± 16 with placebo. The number of patients who achieved complete ulcer closure was six using the combination, four with isosorbide dinitrate, three with chitosan and one with placebo. The progression in the healing process of the ulcer showed marked inmunohistochemical differences of Von Willebrand Factor, desmin, vascular endothelial growth factor-A and α-smooth muscle actin in all groups ( p < 0.001), but without notable differences between them. CONCLUSION: The combination was better than placebo to reduce the dimensions of the ulcer, accelerate healing and increase the number of patients who achieved complete closure of the ulcer, but the combination was not better than chitosan or isosorbide dinitrate used separately.

Effect of Alpha-Lipoic Acid on Clinical and Neurophysiologic Recovery of Carpal Tunnel Syndrome: A Double-Blind, Randomized Clinical Trial.

The objective of our study was to examine the effect of alpha-lipoic acid (ALA) on clinical and neurophysiologic outcomes after surgery for idiopathic carpal tunnel syndrome (CTS). We conducted a randomized, double-blind, placebo-controlled clinical trial in 20 adults diagnosed with idiopathic CTS after clinical and neurophysiologic assessment. Eligible participants took 600 mg ALA or placebo per day for 1 month before surgery, and for 2 months afterward. Further clinical and neurophysiologic assessments were undertaken immediately before surgical decompression, and at 12 weeks postoperatively with additional clinical assessments at the 4th and 8th week after surgery. Clinical outcome measures were taken by Boston Questionnaire score, the presence or absence of Tinel's sign, and Phalen's test findings. Median nerve conduction studies were also undertaken and interpreted according to Dumitru's reference values. Nineteen patients completed the study; one member of the placebo group was lost during follow-up. There were significant improvements in clinical and neurophysiologic variables in the ALA treatment group, present even before surgery. Boston Questionnaire scores had improved significantly in both groups. In the ALA group, none of the participants had positive Phalen's or Tinel's signs at 12 weeks, and motor and sensory fiber latency and amplitude had significantly improved; in the placebo group, only the sensory distal latency had improved significantly. In conclusion, ALA administered 1 month before open decompression and for 2 months afterward improves the clinical and neurophysiologic outcomes after surgery.

Serum levels of P-glycoprotein and persistence of disease activity despite treatment in patients with systemic lupus erythematosus.

Around 25% of patients with systemic lupus erythematosus (SLE) could be refractory to conventional therapies. P-glycoprotein expression on cell surface has been implied on drug resistance, however, to date, it is unknown if P-gp serum levels are associated with SLE disease activity. Evaluate the association of serum P-gp levels and SLE with disease activity despite treatment. A cross-sectional study was conducted on 93 female SLE patients, all receiving glucocorticoids at stable doses for the previous 6 months before to baseline. SLE patients were classified into two groups: (a) patients with active disease [SLE disease activity index (SLEDAI) ≥ 3] despite treatment, and (b) patients with inactive disease (SLEDAI < 3) after treatment. Forty-three healthy females comprised the control group. Serum P-gp, anti-DNA, and both anti-nucleosome antibody levels were measured using ELISA. Active-SLE patients despite treatment had higher P-gp levels compared with inactive-SLE after treatment (78.02 ng/mL ± 114.11 vs. 33.75 ng/mL ± 41.11; p = 0.018) or versus reference group subjects (30.56 ng/mL ± 28.92; p = 0.011). P-gp levels correlated with the scores of SLEDAI (r = 0.26; p = 0.01), Mexican-SLEDAI (MEX-SLEDAI) (r = 0.32; p = 0.002), SLICC/ACR damage index (r = 0.47; p < 0.001), and with prednisone doses (r = 0.33; p = 0.001). In the multivariate model, the high P-gp levels were associated with SLICC/ACR score (p = 0.001), and SLEDAI score (p = 0.014). Our findings support a relationship between serum P-gp levels and SLE with disease activity despite treatment, but it requires further validation in longitudinal studies.

Alternative Interventions to Prevent Oxidative Damage following Ischemia/Reperfusion.

Ischemia/reperfusion (I/R) lesions are a phenomenon that occurs in multiple pathological states and results in a series of events that end in irreparable damage that severely affects the recovery and health of patients. The principal therapeutic approaches include preconditioning, postconditioning, and remote ischemic preconditioning, which when used separately do not have a great impact on patient mortality or prognosis. Oxidative stress is known to contribute to the damage caused by I/R; however, there are no pharmacological approaches to limit or prevent this. Here, we explain the relationship between I/R and the oxidative stress process and describe some pharmacological options that may target oxidative stress-states.

Frecuencia de abortos en familias con un caso de síndrome de Down / Frequency of abortuses in families with an affected of Down syndrome

La ocurrencia de trisomía 21 sólo se ha asociado en forma consistente con la edad materna avanzada. La evidencia de factores genéticos proviene de estudios familiares, consanguinidad y moleculares. Dada la alta ocurrencia de trisomías en abortos de primer trimestre y que la mayoría de las trisomías 21 terminan en abortos, el estudio de la falla reproductiva en familias con un caso de síndrome Down (SD), podría ser un indicador de predisposición a no disminución. Se estudió la ocurrencia de abortos en 48 familias con un caso de trisomía 21 regular y en un grupo control pareado por edad de los padres y orden de gesta, estimando el riesgo de ocurrencia de trisomía 21 ocurrido un primer evento. Se encontró una frecuencia de abortos espontáneos de 9.17 por ciento en el grupo SD y de 2.62 por ciento en el grupo control. La diferencia se mantuvo aún considerando el riesgo de recurrencia de trisomía 21 y fue más marcada en madres de 20-24 años y mayores a 35 años. Nuestros resultados sugieren la existencia de factores intrínsecos, probablemente genético que influyen en la ocurrencia de no disyunción