Bromelain limits airway inflammation in an ovalbumin-induced murine model of established asthma.

CONTEXT: Allergic asthma continues to increase despite new pharmacological advances for both acute treatment and chronic-disease management. Asthma is a multifactorial disease process with genetic, allergic, infectious, environmental, and dietary origins. Researchers are investigating the benefits of lifestyle changes and alternative asthma treatments, including the ability of bromelain to inhibit inflammation. Bromelain is a commonly used, proteolytically active pineapple extract. OBJECTIVE: The present study intended to determine the ability of bromelain to reduce the inflammation of preexisting asthma via an ovalbumin (OVA)-induced murine model of allergic airway disease (AAD). DESIGN: The research team designed a study examining the effects of bromelain in a control group of mice that received phosphate buffered saline (PBS) only and in an intervention group that received bromelain in PBS. Setting The study took place in the Department of Immunology at the University of Connecticut's School of Medicine, Farmington. Intervention The research team sensitized female C57BL/6J mice with intraperitoneal OVA/alum and then challenged them with OVA aerosolization for 10 consecutive days. On day 4, the team began administering daily doses of PBS to the control group (n = 10) and bromelain (6mg/kg) in PBS to the bromelain (intervention) group (n = 10). OUTCOME MEASURES: The primary measures included bronchoalveolar lavage (BAL) cellular differential, cellular phenotype via flow cytometry, and lung histology. Additional outcomes included testing for serum cytokines and immunoglobulin. RESULTS: Bromelain treatment of AAD mice (bromelain group) resulted in significant anti-inflammatory activity as indicated by reduced BAL total leukocytes (P < .05), eosinophils (P < .05), and cellular infiltrates via lung pathology (P < .005), as compared to the control group. In addition, bromelain significantly reduced BAL CD4+ and CD8+ T cells without affecting cell numbers in the spleen or hilar lymph node. The study found decreased interleukins IL-4, IL-12, IL-17, as well as IFN-α in the serum of bromelain-treated animals. CONCLUSIONS: The results suggest that bromelain has a therapeutic effect in established AAD, which may translate into an effective adjunctive therapy in patients with similar conditions, such as allergic asthma, who have chosen to initiate treatment after the onset of symptoms.

Molecular wheels: new Mn12 complexes as single-molecule magnets.

The preparation, structure and magnetic properties of three new wheel-shaped dodecanuclear manganese complexes, [Mn12(Adea)8(CH3COO)14] x 7 CH3CN (1 x 7CH3CN), [Mn12(Edea)8(CH3CH2COO)14] (2) and [Mn12(Edea)8(CH3COO)2(CH3CH2COO)12] (3), are reported, where Adea(2-) and Edea(2-) are dianions of the N-allyl diethanolamine and the N-ethyl diethanolamine ligands, respectively. Each complex has six Mn(II) and six Mn(III) ions alternating in a wheel-shaped topology, with eight n-substituted diethanolamine dianions. All variable-temperature direct current (DC) magnetic susceptibility data were collected in 1, 0.1, or 0.01 T fields and in the 1.8-300 K temperature range. Heat capacity data, collected in applied fields of 0-9 T and in the 1.8-100 K temperature range, indicate the absence of a phase-transition due to long-range magnetic ordering for 1 and 3. Variable-temperature, variable-field DC magnetic susceptibility data were obtained in the 1.8-10 K and 0.1-5 T ranges. All complexes show out-of-phase signals in the AC susceptibility measurements, collected in a 50-997 Hz frequency range and in a 1.8-4.6 K temperature range. Extrapolation to 0 K of the in-phase AC susceptibility data collected at 50 Hz indicates an S = 7 ground state for 1, 2, and 3. Magnetization hysteresis data were collected on a single crystal of 1 in the 0.27-0.9 K range and on single crystals of 2 and 3 in the 0.1-0.9 K temperature range. Discrete steps in the magnetization curves associated with resonant quantum tunneling of magnetization (QTM) confirm these complexes to be single-molecule magnets. The appearance of extra QTM resonances on the magnetic hysteresis of 1 is a result of a weak coupling between two Mn ions at opposite ends of the wheel, dividing the molecule into two ferromagnetic exchange-coupled S = 7/2 halves. The absence of these features on 2 and 3, which behave as rigid spin S = 7 units, is a consequence of different interatomic distances.

Wheel-shaped Mn16 single-molecule magnets.

The syntheses, structures, and magnetic properties of two new single-stranded hexadecanuclear manganese wheels [Mn16(CH3COO)8(CH3CH2CH2COO)8(teaH)12] x 10 MeCN (1 x 10 MeCN) and [Mn16((CH3)2CHCOO)16(teaH)12] x 4 CHCl3 (2 x 4 CHCl3), where teaH(2-) is the dianion of triethanolamine, are reported. 1 crystallizes in the tetragonal I4(1)/a space group [a = b = 33.519(4) A and c = 16.659(2) A]. 2 crystallizes in the monoclinic C2/c space group [a = 21.473(5), b = 26.819(6), c = 35.186(7), and beta = 93.447(5) degrees]. Both complexes consist of 8 Mn(II) and 8 Mn(III) ions alternating in a wheel-shaped topology with 12 monoprotonated triethanolamine ligands. Variable-temperature direct current (DC) magnetic susceptibility data were collected in 1 T, 0.1 and 0.01 T fields, and in the 1.8-300 K temperature range for 1 and 2. Variable-temperature variable-field DC magnetic susceptibility data were obtained in the 1.8-10 K and 0.1-5 T ranges and least-squares fitting of these reduced magnetization versus H/T data indicates a S = 13 ground-state for 1 and 2. Single-crystal magnetization hysteresis measurements were performed in a 0.04-1 K temperature range for complex 2. Hysteresis loops were observed that showed a temperature dependence, which indicates that 2 exhibits magnetization relaxation and is a SMM. Both 1 and 2 show frequency-dependent out-of-phase signals in the AC susceptibility measurements, collected in a temperature range of 1.8-5 K and in the frequency range of 50-10,000 Hz. Extrapolation of the in-phase component of the AC susceptibility data to 0 K indicates an S = 12 ground state for 1 and an S = 11 ground-state for 2. Complex 1 has the highest-spin ground state reported to date for a single-stranded manganese wheel and is likely to be an SMM based on a frequency-dependent out-of-phase signal in the AC susceptibility. The AC susceptibility as well as magnetization hysteresis data for 2 confirm that this species is an SMM.

Wheel-shaped [Mn12] single-molecule magnets.

The reaction of [Mn(12)O(12)(O(2)CCH(3))(16)(H(2)O)(4)].4H(2)O.2CH(3)COOH with n-methyldiethanol amine (H(2)mdea), n-ethyldiethanol amine (H(2)edea), or n-butyldiethanol amine (H(2)bdea) leads to the formation of wheel-shaped Mn(III)(6)Mn(II)(6) complexes with the general formula [Mn(12)(R)(O(2)CCH(3))(14)] (1, R = mdea; 2, R = edea; and 3, R = bdea). Complex 1 crystallizes in the triclinic space group P1, whereas complex 3 crystallizes in the monoclinic space group C(2/c). Complex 1a has the same molecular structure as complex 1 but crystallizes in the monoclinic space group P2(1/n). Complex 3a has the same molecular structure as complex 3 but crystallizes in the triclinic space group P1. Variable-temperature magnetic susceptibility data collected for complexes 1, 2, and 3 indicate that antiferromagnetic exchange interactions are present. The spin ground states of complexes 1, 2, and 3 were determined by fitting variable-field magnetization data collected in the 2-5 K temperature range. Fitting of these data yielded the spin ground-state parameters of S = 8, g = 2.0, and D = -0.47 cm(-1) for complex 1; S = 8, g = 2.0, and D = -0.49 cm(-1) for complex 2; and S = 8, g = 2, and D = -0.37 cm(-1) for complex 3. The ac magnetic susceptibility data were measured for complexes 1, 2, and 3 at temperatures between 1.8 and 10 K with a 3 G ac field oscillating in the range 50-1000 Hz. Slow kinetics of magnetization reversal relative to the frequency of the oscillating ac field were observed as frequency-dependent out-of-phase peaks for complexes 1, 2, and 3, and it can be concluded that these three complexes are single-molecule magnets.