pH Manipulation as a Novel Strategy for Treating Mucormycosis

Mucormycosis is a fatal fungal disease caused by several organisms within the order Mucorales. In recent years, traumatic injury has emerged as a novel risk factor for mucormycosis. Current antifungal therapy is ineffective, expensive, and typically requires extensive surgical debridement. There is thus a pressing need for safe prophylactic treatment that can be rapidly and easily applied to high-risk patients, such as those with major trauma injuries. Acetic acid has been used as a topical treatment for burn wounds for centuries and has proven activity against Gram-negative bacteria. Here, we demonstrate that acetic acid is also highly effective against major pathogenic groups of Mucorales, even at very low concentrations (0.3%). This antifungal effect is not seen with other acids, such as hydrochloric and lactic acid, suggesting that acetic acid activity against Mucorales spores is not solely evoked by low environmental pH. In agreement with this, we demonstrate that the antifungal activity of acetic acid arises from a combination of its ability to potently lower intracellular pH and from pH-independent toxicity. Thus, dilute acetic acid may offer a low-cost, safe, prophylactic treatment for patients at risk of invasive mucormycosis following traumatic injury.     

Influenza: the reemergence of an ancient disease and its risk of pandemia

Influenza is a seasonally, acute respiratory disease, highly transmissible. The diversity of the natural reservoirs of influenza A virus and its faculty of reassortment increase the risk of a new pandemia. Prevention strategies during the outbreaks include vaccination indicated to risk population as infants between 6 to 2 years old, persons above 65 years old, pregnant women and patients with underlying diseases. Antiviral prophylaxis is useful to control small outbreaks and to be used in household contacts of risk population who have not been vaccinated. Antiviral drugs as a treatment should be considered in persons with severe disease. During a pandemia these prevention measures must be reinforced and rational use of antiviral drugs and vaccine with the pandemic strain should be emphasized.     

Effects of ethyl pyruvate on leukocyte-endothelial interactions in the mesenteric microcirculation during early sepsis treatment

OBJECTIVES:Experimental studies on sepsis have demonstrated that ethyl pyruvate is endowed with antioxidant and anti-inflammatory properties. This study aimed to investigate the effects of ethyl pyruvate on leukocyte-endothelial interactions in the mesenteric microcirculation in a live Escherichia coli-induced sepsis model in rats.METHODS:Male Wistar rats were administered an intravenous suspension of E. coli bacteria or were subjected to a sham procedure. Three hours after bacterial infusion, the rats were randomized into the following groups: a control group without treatment, a group treated with lactated Ringer''s solution (4 mL/kg, i.v.), and a group treated with lactated Ringer''s solution (4 mL/kg, i.v.) plus ethyl pyruvate (50 mg/kg). At 24 h after bacterial infusion, leukocyte-endothelial interactions were investigated using intravital microscopy, and the expression of P-selectin and intercellular adhesion molecule-1 was evaluated via immunohistochemistry. White blood cell and platelet counts were also determined at baseline and 3 h and 24 h after E. coli inoculation.RESULTS:The non-treated and lactated Ringer''s solution-treated groups exhibited increases in the numbers of rolling leukocytes (∼2.5-fold increase), adherent cells (∼3.0-fold), and migrated cells (∼3.5-fold) compared with the sham group. In contrast, treatment with Ringer''s ethyl pyruvate solution reduced the numbers of rolling, adherent and migrated leukocytes to the levels observed in the sham group. Additionally, the expression of P-selectin and intercellular adhesion molecule-1 was significantly increased on mesenteric microvessels in the non-treated group compared with the sham group (p<0.001). The expression of both adhesion molecules was reduced in the other groups, with ethyl pyruvate being more effective than lactated Ringer''s solution. Infusion of bacteria caused significant leukopenia (3 h), followed by leukocytosis with granulocytosis (24 h). There was also an intense and progressive reduction in the number of platelets. However, no differences were observed after treatment with the different solutions.CONCLUSIONS:The presented data suggest that ethyl pyruvate efficiently reduces the inflammatory response in the mesenteric microcirculation in an experimental model of sepsis induced by live E. coli and is associated, at least in part, with down-regulation of P-selectin and intercellular adhesion molecule-1.     

Determinants of Functional and Structural Properties of Large Arteries in Healthy Individuals

Background

Changes in the properties of large arteries correlate with higher cardiovascular risk. Recent guidelines have included the assessment of those properties to detect subclinical disease. Establishing reference values for the assessment methods as well as determinants of the arterial parameters and their correlations in healthy individuals is important to stratify patients.

Objective

To assess, in healthy adults, the distribution of the values of pulse wave velocity, diameter, intima-media thickness and relative distensibility of the carotid artery, in addition to assessing the demographic and clinical determinants of those parameters and their correlations.

Methods

This study evaluated 210 individuals (54% women; mean age, 44 ± 13 years) with no evidence of cardiovascular disease. The carotid-femoral pulse wave velocity was measured with a Complior^® device. The functional and structural properties of the carotid artery were assessed by using radiofrequency ultrasound.

Results

The means of the following parameters were: pulse wave velocity, 8.7 ± 1.5 m/s; diameter, 6,707.9 ± 861.6 μm; intima-media thickness, 601 ± 131 μm; relative distensibility, 5.3 ± 2.1%. No significant difference related to sex or ethnicity was observed. On multiple linear logistic regression, the factors independently related to the vascular parameters were: pulse wave velocity, to age (p < 0.01) and triglycerides (p = 0.02); intima-media thickness, to age (p < 0.01); diameter, to creatinine (p = 0.03) and age (p = 0.02); relative distensibility, to age (p < 0.01) and systolic and diastolic blood pressures (p = 0.02 and p = 0.01, respectively). Pulse wave velocity showed a positive correlation with intima media thickness (p < 0.01) and with relative distensibility (p < 0.01), while diameter showed a positive correlation with distensibility (p = 0.03).

Conclusion

In healthy individuals, age was the major factor related to aortic stiffness, while age and diastolic blood pressure related to the carotid functional measure. The carotid artery structure was directly related to aortic stiffness, which was inversely related to the carotid artery functional property.     

Prognostic Value of TIMI Score versus GRACE Score in ST-segment Elevation Myocardial Infarction

Background

The TIMI Score for ST-segment elevation myocardial infarction (STEMI) was created and validated specifically for this clinical scenario, while the GRACE score is generic to any type of acute coronary syndrome.

Objective

Between TIMI and GRACE scores, identify the one of better prognostic performance in patients with STEMI.

Methods

We included 152 individuals consecutively admitted for STEMI. The TIMI and GRACE scores were tested for their discriminatory ability (C-statistics) and calibration (Hosmer-Lemeshow) in relation to hospital death.

Results

The TIMI score showed equal distribution of patients in the ranges of low, intermediate and high risk (39 %, 27 % and 34 %, respectively), as opposed to the GRACE Score that showed predominant distribution at low risk (80 %, 13 % and 7%, respectively). Case-fatality was 11%. The C-statistics of the TIMI score was 0.87 (95%CI = 0.76 to 0.98), similar to GRACE (0.87, 95%CI = 0.75 to 0.99) - p = 0.71. The TIMI score showed satisfactory calibration represented by χ2 = 1.4 (p = 0.92), well above the calibration of the GRACE score, which showed χ2 = 14 (p = 0.08). This calibration is reflected in the expected incidence ranges for low, intermediate and high risk, according to the TIMI score (0 %, 4.9 % and 25 %, respectively), differently to GRACE (2.4%, 25% and 73%), which featured middle range incidence inappropriately.

Conclusion

Although the scores show similar discriminatory capacity for hospital death, the TIMI score had better calibration than GRACE. These findings need to be validated populations of different risk profiles.