Modulation of polymorphonuclear leukocyte responsiveness by copper (II)2 (niflumate)4

Antiinflammatory activities and modulations of PMNL responses produced by treatment with tetrakis--2-[3-(trifluoromethyl)-phenyl] aminonicotinatodicopper (II) [Cu(II)₂(niflumate)₄] and niflumic acid were studied in isologous serum-induced rat pleurisy. Doses of 10 or 30 mg/kg (35 or 106 µmol/kg) of niflumic acid or Cu(II)₂ (niflumate)₄ (8 or 23 µmol/kg) caused significant (p < 0.01) reductions in pleural exudate and number of polymorphonuclear leukocytes (PMNLs) in the exudate. While both doses of Cu(II)₂(niflumate)₄ produced significant dose-related reductions in both parameters, only the higher dose of niflumic acid produced a significant dose-related reduction in both parameters. Boyden chamber measurements of N-formyl-methionyl-leucyl-phenylalanine (f-MLP) chemotaxis by PMNLs incubated with 10 or 30 µg/ml niflumic acid (35 or 106 nmol/ml) or Cu(II)₂(niflumate)₄ (8 or 23 nmol/ml) were significantly (p < 0.01 to p < 0.001) decreased in dose-related fashions. Chemotaxis of PMNLs from pleuritic rats treated orally with 10 or 30 mg/kg niflumic acid or Cu(II)₂(niflumate)₄ was significantly (p < 0.001) inhibited by the larger dose of niflumic acid and both doses of Cu(II)₂(niflumate)₄. Opsonized zymosan (OZ)-stimulated chemiluminescence (CL) of PMNLs from pleuritic rats treated orally with these same doses of niflumic acid or Cu(II)₂(niflumate)₄ was only significantly (p < 0.05 or p < 0.01 respectively) decreased by the larger doses. Superoxide (O ₂ ^- ) production by these cells was significantly decreased by the larger dose of niflumic acid (p < 0.05) while both doses of Cu(II)₂(niflumate)₄ produced significant (p < 0.05 to p < 0.01) decreases. Recovery of the decreased PMNL response in burned rats was also studied following treatment with these two compounds. Oral treatment of non-burned rats with 1 mg/kg niflumic acid (4 µmol/kg) or Cu(II)₂(niflumate)₄ (1 µmol/kg) did not affect OZ-stimulated O ₂ ^- production while decreased O ₂ ^- production in non-treated scald-burned rats was reversed by oral treatment with either niflumic acid or Cu(II)₂(niflumate)₄. It is concluded that Cu(II)₂(niflumate)₄ is a more effective antiinflammatory agent than niflumic acid and more effective modulation of PMNL responsiveness may explain its beneficial antipleuritic and burn-injury recovery effects. Formation of the copper complex of niflumic acidin vivo may also account for its beneficial antiinflammatory effects and recovery of depressed PMNL responsiveness in burned rats.     

Effect of chronic treatment with bovine recombinant growth hormone on cardiac dysfunction and lesion progression in UM-X7.1 cardiomyopathic hamsters

In view of the potentially beneficial effect of GH on ventricular function of humans suffering from idiopathic dilated cardiomyopathy, we undertook a study to evaluate the optimal time to initiate treatment with GH and its duration in UM-X7.1 cardiomyopathic hamsters (CMH). GH (1 mg/kg.d) therapy was initiated either in the early or late (30 and 160 d old, respectively) phases of the disease and continued until death at 240 d of age. Age- and sex-matched Golden Syrian hamsters (GSH) were used as controls. Basal IGF-1 levels in serum were reduced by nearly half in CMH compared with GSH but were increased within a physiological range in male hamsters. In contrast, female hamsters presented elevated basal serum IGF-1 levels that were not further elevated by GH administration, as reported in experimental models and humans. Accordingly, the present study will focus on the effects of GH therapy on cardiac performance in male hamsters. GH did not improve ventricular function when starting at a late stage of the disease compared with CMH controls. Maximum rate of left ventricular pressure development decreased by approximately 64% in CMH treated early with recombinant bovine GH. Ventricular dysfunction was associated with morphologic indices of hypertrophy, ventricular dilatation, and extensive fibrosis. Mortality was strikingly increased in GH-treated CMH for 210 d (four males and eight females), as opposed to four females (and no male) in the vehicle-treated group. These results suggest that chronic treatment with recombinant bovine GH in CMH, starting at an early stage of lesion development, is associated with a reduced cardiac performance at the terminal stage of the disease.     

Histopathological studies in two strains of semi-immune mice infected with Plasmodium berghei ANKA after chronic exposure

To mimic a human malaria infection in the endemic condition, two strains of mice (Balb/c and CBA) were infected and treated several times to generate so-called semi-immune status. As previously reported, neither mice (Balb/c and CBA) strain showed cerebral malaria, even in the susceptible C57BL/6 (B6). The significant difference between the mice strains in our previous study was the rate of destruction of uninfected red blood cells (uRBCs) at infection. After the established repeated cycles of infection and treatment and the final challenge with 10⁴ Plasmodium berghei ANKA until minimum Hb, Balb/c and CBA mice were sacrificed. The spleen, liver, brain, kidney, lung, heart, and muscle were removed, stained with hematoxylin–eosin and analyzed with light microscopy. Previous observation suggested that Balb/c destroyed uRBC at much higher rate than the other strains although the parasitemia was very low. Pathological investigation carried out in this study revealed that this destruction was mainly contributed by the uRBCs as no parasite sequestration was observed in any of the organs. However, malaria pigment deposition was observed in spleen and liver of all the semi-immune mice strains. This histopathological study in the severe malaria anemia model, which is difficult to conduct in humans, will be helpful in taking into account different responses to malaria infection when designing therapeutic interventions and vaccine studies.     

Effect of an equine-movement therapy program on gait, energy expenditure, and motor function in children with spastic cerebral palsy: a pilot study

The purpose of this study was to evaluate the effects of an 8-week program of hippotherapy on energy expenditure during walking; on the gait dimensions of stride length, velocity, and cadence; and on performance on the Gross Motor Function Measure (GMFM) in five children with spastic cerebral palsy (CP). A repeated-measures within-subjects design was used consisting of two baseline measurements taken 8 weeks apart, followed by an 8-week intervention period, then a posttest. After hippotherapy, all five children showed a significant decrease (X_r²;=7.6, P<0.05) in energy expenditure during walking and a significant increase (X_r²=7.6, P<0.05) in scores on Dimension E (Walking, Running, and Jumping) of the GMFM. A trend toward increased stride length and decreased cadence was observed. This study suggests that hippotherapy may improve energy expenditure during walking and gross motor function in children with CP.     

Old measures and new scores in spinal muscular atrophy patients

Introduction: A recent Rasch analysis performed on the Hammersmith Functional Motor Scale—Expanded (HFMSE) in patients with spinal muscular atrophy (SMA) identified issues impacting scale validity, redundant items, and disordered thresholds on some items. Methods: We modified the HMFSE scoring based on the Rasch analysis and on expert consensus to establish whether the traditional scoring overestimated the number of patients with changes within 2 points from baseline. Data were collected retrospectively from multicenter data sets in 255 type 2 and 3 SMA patients. Results: The mean 12‐month changes using the new and the traditional scoring system did not differ significantly (P > 0.05). The numbers of patients who improved or decreased by >2 points were also similar. Conclusions: The presence of outliers using the traditional scoring system was not due to overestimation of changes in activities that were tested bilaterally or to discrepancies in the scoring hierarchy of individual items. Muscle Nerve 52:435–437, 2015