Antibacterial activity and inhibition against Staphylococcus aureus NorA efflux pump by ferulic acid and its esterified derivatives

Objective: To evaluate the inhibitory activity of ferulic acid and four of its esterified derivatives (methyl, ethyl, propyl, and butyl) against resistance mech...     

New Compounds Hybrids 1H‐1,2,3‐Triazole‐Quinoline Against Plasmodium falciparum

Malaria is one of the most prevalent parasitic diseases in the world. The global importance of this disease, current vector control limitations, and the absence of an effective vaccine make the use of therapeutic antimalarial drugs the main strategy to control malaria. Chloroquine is a cost‐effective antimalarial drug with a relatively robust safety profile, or therapeutic index. However, chloroquine is no longer used alone to treat patients with Plasmodium falciparum due to the emergence and spread of chloroquine‐resistant strains, which have also been reported for Plasmodium vivax. However, the activity of 1,2,3‐triazole derivatives against chloroquine‐sensitive and chloroquine‐resistant strains of P. falciparum has been reported in the literature. To enhance the anti‐P. falciparum activity of quinoline derivatives, we synthesized 11 new quinoline‐1H‐1,2,3‐triazole hybrids with different substituents in the 4‐positions of the 1H‐1,2,3‐triazole ring, which were assayed against the W2‐chloroquine‐resistant P. falciparum clone. Six compounds exhibited activity against the P. falciparum W2 clone, chloroquine‐resistant, with IC₅₀ values ranging from 1.4 to 46 μm . None of these compounds was toxic to a normal monkey kidney cell line, thus exhibiting good selectivity indexes, as high 351 for one compound ( 11 ).     

Surgical-site infection risk in oncologic digestive surgery

Surgical-site infection (SSI) is the most prevalent type of hospital infection in surgical patients and is associated with an increase in hospital stay, costs and morbidity/lethality. The knowledge of the main risk factors for this type of infection is important for the establishment of prevention measures regarding modifiable risks factors. The objective of the preset study was to assess the occurrence of SSI and study the risk factors in oncologic surgeries of the digestive system at Hospital de Câncer in Barretos, São Paulo, Brazil. Individuals undergoing oncologic surgeries of the digestive system in the period of 08/01/2007 to 08/10/2008 were prospectively followed for 30 days after surgery. Possible risk factors related to the patient and to the surgical procedure were also studied. A total of 210 surgeries were analyzed, with a global SSI incidence of 23.8%. The following variables were independently associated with SSI: time and type of surgery, radiotherapy before surgery and surgeon's years of experience. The risk factors found in this study have been described by other authors and are not amenable to intervention for SSI prevention. Further studies are recommended with the objective of investigating interventions that could reduce the risk for SSI in this type of surgery.     

Blockade of CXCR1/2 chemokine receptors protects against brain damage in ischemic stroke in mice: Ischemia and Reparixin

OBJECTIVE:

Ischemic stroke may result from transient or permanent reductions of regional cerebral blood flow. Polymorphonuclear neutrophils have been described as the earliest inflammatory cells to arrive in ischemic tissue. CXCR1/2 receptors are involved in the recruitment of these cells. However, the contribution of these chemokine receptors during transient brain ischemia in mice remains poorly understood. In this work, we investigated the effects of reparixin, an allosteric antagonist of CXCR1/2 receptors, in a model of middle cerebral artery occlusion and reperfusion in mice.

METHODS:

C57BL/6J male mice treated with reparixin or vehicle were subjected to a middle cerebral artery occlusion procedure 1 h after the treatment. Ninety minutes after ischemia induction, the monofilament that prevented blood flow was removed. Twenty-four hours after the reperfusion procedure, behavioral changes, including motor signs, were analyzed with the SmithKline/Harwell/Imperial College/Royal Hospital/Phenotype Assessment (SHIRPA) battery. The animals were sacrificed, and brain tissue was removed for histological and biochemical analyses. Histological sections were stained with hematoxylin and eosin, neutrophil infiltration was estimated by myeloperoxidase activity and the inflammatory cytokine IL-1β was measured by ELISA.

RESULTS:

Pre-treatment with reparixin reduced the motor deficits observed in this model of ischemia and reperfusion. Myeloperoxidase activity and IL-1β were reduced in the reparixin-treated group. Histological analysis revealed that ischemic injury was also attenuated by reparixin pre-treatment.

CONCLUSIONS:

Our results suggest that the blockade of the CXCR1/2 receptors by reparixin promotes neuroprotective effects by reducing the levels of polymorphonuclear infiltration in the brain and the tissue damage associated with middle cerebral artery occlusion and reperfusion.     

Predictors of Excess Weight Loss in Obese Patients After Gastric Bypass: a 60-Month Follow-up

Background

The objective of this study was to analyze the factors associated with change in body mass index (BMI) and with percentage of excess weight loss (%EWL) in patients undergoing Roux-en-Y gastric bypass (RYGB). The following factors were analyzed: sex, age, surgical access (laparotomy vs. laparoscopy), preoperative BMI, waist circumference (WC), type 2 diabetes mellitus (T2DM), high blood pressure, and dyslipidemia.

Methods

Retrospective cohort study using a convenience sample of 2070 patients of both sexes, aged 18 to 65 years, undergoing RYGB between 2000 and 2013. The outcomes of interest were BMI and %EWL at 0, 6, 12, 18, 24, 30, 36, 42, 48, 54, and 60 months after RYGB.

Results

After 36, 48, and 60 months, approximately 50 % of patients had BMI >30 kg/m². As for %EWL, 60-month results were poor for 17 % of patients (%EWL <50 %), good for 40 % of patients (%EWL 50–75 %), very good for 24 % of patients (%EWL from >75–90 %), and excellent for 19 % of patients (%EWL >90 %). The four most significant predictors of BMI change 60 months after RYGB (in descending order of magnitude) were preoperative BMI, preoperative WC, surgical access, and age; and of %EWL, surgical access, preoperative BMI, preoperative WC, and age.

Conclusions

After 60 months of follow-up, the most relevant predictors of weight loss after RYGB were lower preoperative BMI and WC, videolaparoscopy as surgical access, and younger age. Further studies must be carried out to elucidate the impact of these factors on RYGB outcomes.

     

Effect of fibronectin on proteasome activity, acrosome reaction, tyrosine phosphorylation and intracellular calcium concentrations of human sperm

BACKGROUND: Previously we showed that the human sperm proteasome plays significant roles during mammalian fertilization. Here we studied the effect of fibronectin (Fn), an extracellular matrix protein present in the cumulus oophorus of the oocyte, on proteasome activity, acrosome reaction, intracellular calcium concentration ([Ca(2+)](i)) and protein tyrosine phosphorylation of human sperm. METHODS: Aliquots of motile sperm were incubated for 15 min (T0), 5 h (T5) and 18 h (T18), at 37 degrees C, 5% CO(2) and 95% air with Fn (0-100 microg/ml). The chymotrypsin- and trypsin-like activity of the proteasome was measured using the fluorogenic substrates, Suc-Leu-Leu-Val-Tyr-AMC and Boc-Gln-Ala-Arg-AMC, respectively. At T18, sperm aliquots were incubated for 15 min with Fn and/or progesterone in the presence or absence of epoxomicin (a proteasome inhibitor). The percentage of viable acrosome reacted sperm was evaluated using the Fluorescein isothiocyanate (FITC)-labeled Pisum sativum agglutinin. Tyrosine phosphorylation was evaluated by western blot and [Ca(2+)](i) using fura 2. RESULTS: Fn stimulated both enzymatic activities of the proteasome and the acrosome reaction of human sperm. Progesterone enhanced and epoxomicin drastically inhibited the effect of Fn. Fn treatment also increased the [Ca(2+)](i). Western blot analysis revealed that Fn increased tyrosine protein phosphorylation and that some proteasome subunits became tyrosine phosphorylated upon Fn treatment. CONCLUSIONS: These results suggest that Fn activates the proteasome and induces the acrosome reaction in human sperm. This effect may involve binding with specific receptors (integrins) on the sperm surface and the activation of tyrosine kinases.     

Hypoglycemia incidence and awareness among insulin-treated patients with diabetes: the HAT study in Brazil

Background

Hypoglycemia affects patient safety and glycemic control during insulin treatment of both type 1 (T1DM) and type 2 diabetes mellitus (T2DM). The Hypoglycemia Assessment Tool study in Brazil aimed to determine the proportion of patients experiencing hypoglycemic events and to characterize patient awareness and fear about hypoglycemia, among insulin-treated T1DM or T2DM patients.

Methods

This was a non-interventional, multicenter study, with a 6-month retrospective and a 4-week prospective evaluation of hypoglycemic events. Patients completed a questionnaire at baseline and at the end of the study, and also a patient diary. The answers ‘occasionally’ and ‘never’ to the question ‘Do you have symptoms when you have a low sugar level?’ denoted impaired hypoglycemia awareness. Fear was reported on a 10-point scale, from ‘not afraid at all’ to ‘absolutely terrified’.

Results

From 679 included patients, 321 with T1DM and 293 T2DM, median age of 33.0 and 62.0 years, 59% and 56% were female, and median diabetes duration was 15.0 and 15.0 years, respectively. Median time of insulin use was 14.0 and 6.0 years. During the prospective period, 91.7% T1DM and 61.8% T2DM patients had at least one hypoglycemic event. In the same period, 54.0% T1DM and 27.4% T2DM patients had nocturnal hypoglycemia, 20.6% T1DM and 10.6% T2DM patients had asymptomatic hypoglycemia, and severe events occurred in 20.0% and 10.3%, respectively. At baseline, 21.4% T1DM and 34.3% T2DM had hypoglycemia unawareness. The mean score of hypoglycemia fear was 5.9?±?3.1 in T1DM and 5.4?±?3.9 in T2DM. The most common attitude after hypoglycemic events were to increase calorie intake (60.3%) and blood glucose monitoring (58.0%) and to reduce or skip insulin doses (30.8%).

Conclusions

Referred episodes of hypoglycemia were high, in both T1DM and T2DM insulin users. Patient attitudes after hypoglycemia, such as reduction in insulin and increase in calorie intake, can affect diabetes management. These findings may support clinicians in tailoring diabetes education and insulin treatment for patients with diabetes, in order to improve their glycemic control while reducing the risk of hypoglycemic events.