Synthesis of 3- or 4-phenyl-1,8-naphthyridine derivatives and evaluation of antimycobacterial and antimicrobial activity

A series of 3- or 4-phenyl-1,8-naphthyridine derivatives variously substituted in the positions 2, 6 and 7 were synthesized and evaluated for in vitro evaluation for their antimycobacterial activity as part of a TAACF TB screening program under the direction of the US National Institute of Health, NIAID division. Several compounds showed an interesting activity when tested at a concentration of 6.25 microg/ml against Mycobacterium tuberculosis H(37)Rv and in particular compounds 2a, 4a,d, 8a,d and 8i, exhibit a % inhibition from 91 to 99. Among these, compounds 2a, 8a and 8d appeared to have a good activity with minimum inhibitory concentrations (MICs) of 6.25 microg/ml. On the basis of the biological results, the most effective substituent in position 2 or 7 seems to be the piperidinyl group. The introduction of a morpholinyl group either in position 2 or 7 of the heterocycle ring caused a decrease in activity. The 1,8-naphthyridine derivatives were also tested in vitro for their antimicrobial activity against Staphylococcus aureus as Gram-positive bacteria and Escherichia coli as Gram-negative bacteria.     

A multiple-micronutrient-fortified beverage affects hemoglobin, iron, and vitamin A status and growth in adolescent girls in rural Bangladesh

Adolescent girls have high nutrient needs and are susceptible to micronutrient deficiencies. The objective of this study was to test the effect of a multiple-micronutrient-fortified beverage on hemoglobin (Hb) concentrations, micronutrient status, and growth among adolescent girls in rural Bangladesh. A total of 1125 girls (Hb > or = 70 g/L) enrolled in a randomized, double-blind, placebo-controlled trial and were allocated to either a fortified or nonfortified beverage of similar taste and appearance. The beverage was provided at schools 6 d/wk for 12 mo. Concentrations of Hb and serum ferritin (sFt), retinol, zinc, and C-reactive protein were measured in venous blood samples at baseline, 6 mo, and 12 mo. In addition, weight, height, and mid-upper arm circumference (MUAC) measurements were taken. The fortified beverage increased the Hb and sFt and retinol concentrations at 6 mo (P < 0.01). Adolescent girls in the nonfortified beverage group were more likely to suffer from anemia (Hb <120 g/L), iron deficiency (sFt <12 microg/L), and low serum retinol concentrations (serum retinol <0.70 micromol/L) (OR = 2.04, 5.38, and 5.47, respectively; P < 0.01). The fortified beverage group had greater increases in weight, MUAC, and BMI over 6 mo (P < 0.01). Consuming the beverage for an additional 6 mo did not further improve the Hb concentration, but the sFt level continued to increase (P = 0.01). The use of multiple-micronutrient-fortified beverage can contribute to the reduction of anemia and improvement of micronutrient status and growth in adolescent girls in rural Bangladesh.     

Isolation and Identification of E. cowanii from Powdered Infant Formula in NICU and Determination of Antimicrobial Susceptibility of Isolates

Objective: Enterobacter cowanii is a genus of common gram-negative, facultatively anaerobic, rod-shaped, non-spore-forming bacterium of the Enterobacteriaceae family. This organism can be potentially a powdered infant milk formula-borne opportunistic pathogen. The aim of this study was to isolate and identify E. cowanii from consumed powdered infant formula milk (PIF) in intensive care units (NICU) and to determine antimicrobial susceptibility patterns of this bacterium. Methods: E. cowanii was isolated according to FDA method in 125 samples of PIF milk purchased from drug stores between Jun 2011 and March 2012. For final confirmation, biochemical tests embedded in API-20E system were used. The drug susceptibility test was performed using the disc diffusion method according to CLSI recommendations. Findings : Out of the 125 PIF samples investigated, 4 (3.2%) samples were positive for E. cowanii. All four isolates from PIF samples were uniformly susceptible to imipenem, meropenem, ceftazidime, ciprofloxacin, and colistin. Fifty percent of isolates were resistant to ampicillin, amoxicillin, and cotrimoxazole Conclusion: Analysis of the results indicated that complementary studies are necessary to clarify the possible role of E. cowanii as a food contaminant, in common NICU infections and high risk groups including persons with underlying disease and immunocompromised individuals.Key Words: Powdered Infant Formula Milk; Neonatal Intensive Care Unit; E. Cowanii; Antimicrobial Susceptibility     

Is the knowledge of contact force beneficial in pulmonary vein antrum isolation?

Objective: To investigate the effect of the operator knowing the real-time contact force (CF) on the efficacy of pulmonary vein antrum isolation (PVAI).

Methods: Fifty patients with paroxysmal atrial fibrillation (AF) or short lasting persistent AF were randomized to CF guided PVAI (n?=?25) or conventional PVAI (n?=?25). In the CF guided group, CF between 10 and 40?g was aimed at. Efficacy of PVAI was measured as reduction in AF burden (AFB) and time to AF recurrence detected by implantable cardiac monitor (ICM), inserted three months before PVAI. Blanking period was three months and follow-up 12 months.

Results: All pulmonary veins were isolated in the CF guided group and all but one in the conventional group. Mean CF was 25?g in the CF guided group and 24?g in the conventional group (p?=?0.75). Compared to pre-ablation, median [IQR] relative reduction in AFB 3–12 months after ablation was 100 [99–100]% in the CF guided group (p?p?p?=?0.09). Nine patients (36%) had AF recurrence in the CF guided group and 13 (52%) in the conventional group (p?=?0.21, log-rank test). CF differed between operators. When adjusted for operator by regression analysis, patients without recurrent AF had lower proportion of ablation time with CF <10?g than recurrent patients (p?=?0.034). No complications occurred.

Conclusions: Operator knowledge of real-time CF had no significant effect on AFB reduction or time to AF recurrence. Larger trials should be done to study benefit of real-time CF.     

Investigating the Antiangiogenic,Anti-drug Resistance and Apoptotic Effects of Soy Isoflavone Extract Alone or in Combination with Docetaxel on Murine 4T1 Breast Tumor Model

Background: One major concern in the treatment of cancer patients during chemotherapy is drug resistance. Here we investigated the effects of soy isoflavone extracts alone or in combination with Docetaxel on the drug resistance, angiogenesis, apoptosis, and tumor volume in mouse 4T1 breast tumor model. Methods: Sixty female BALB/c mice were randomly divided into 4 groups: control, dietary soy isoflavone extract [Iso, 100 mg/kg diet (0.01%)], Docetaxel (10 mg/kg) injection, and the combination of dietary soy isoflavone extract and intravenous Docetaxel injection (Docetaxel + Iso). One week after the third injection, the breast tumors of eight mice from each group were excised to analyze NF-κBp65′ vascular endothelial growth factor receptor-2 (VEGFR2) and Pgp gene and protein expressions and the other seven mice were monitored for survival rate analysis until they died. Results: NF-κBp65 gene and protein expressions were significantly lower in the Docetaxel + Iso group in comparison with that of the Docetaxel group. VEGFR2 protein expression in the Docetaxel + Iso and Iso groups was significantly lower than that of the Docetaxel group. Conclusion: These findings may indicate that the combined use of isoflavone extracts together with chemotherapeutic agents has more efficient anti-carcinogenic effects than their individual use.     

Protective effect of soy protein on collagen-induced arthritis in rat

To evaluate preventive and therapeutic effects of soy protein on collagen-induced arthritis rats. Sprague–Dawley rats immunized with bovine type II collagen emulsified in adjuvant and treated with soy protein (7?g/kg), dexamethasone (1?mg/kg), and casein (in control groups) by daily gavages feedings for 30?days. Score of arthritis recorded every day for each paws of animal. Tumor necrosis factor-alpha, interleukin6, leptin, and adiponectin were measured in serums. Treatment with soy protein resulted in significant delay in time to onset of arthritis as well as significantly decreased arthritis incidence, clinical arthritis severity score, histopathological arthritis severity score, and in vivo cell-mediated immunity to collagen (P?<?0.05). Administration of soy protein significantly suppressed the progression of collagen II-induced arthritis and inhibited the production of tumor necrosis factor-alpha, interleukin6, leptin, and adiponectin. Soy protein appeared to be a potent immunomodulatory inhibitor of collagen II-induced arthritis in rats. It could delay onset of RA and reduced cartilage erosion and synovitis inflammation. Therefore, it may be a useful protein in the prevention and treatment of rheumatoid arthritis patient.