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61.
John Lasekan Yong Choe Svyatoslav Dvoretskiy Amy Devitt Sue Zhang Amy Mackey Karyn Wulf Rachael Buck Christine Steele Michelle Johnson Geraldine Baggs 《Nutrients》2022,14(13)
Background: Five of the most abundant human milk oligosaccharides (HMOs) in human milk are 2′-fucosyllactose (2′-FL), 3-fucosyllactose (3-FL), lacto-N-tetraose (LNT), 3′-sialyllactose (3′-SL) and 6′-sialyllactose (6′-SL). Methods: A randomized, double-blind, controlled parallel feeding trial evaluated growth in healthy term infants fed a control milk-based formula (CF; n = 129), experimental milk-based formula (EF; n = 130) containing five HMOs (5.75 g/L; 2′-FL, 3-FL, LNT, 3′-SL and 6′-SL) or human milk (HM; n = 104). Results: No significant differences (all p ≥ 0.337, protocol evaluable cohort) were observed among the three groups for weight gain per day from 14 to 119 days (D) of age, irrespective of COVID-19 or combined non-COVID-19 and COVID-19 periods. There were no differences (p ≥ 0.05) among the three groups for gains in weight and length from D14 to D119. Compared to the CF group, the EF group had more stools that were soft, frequent and yellow and were similar to the HM group. Serious and non-serious adverse events were not different among groups, but more CF-fed infants were seen by health care professionals for illness from study entry to D56 (p = 0.044) and D84 (p = 0.028) compared to EF-fed infants. Conclusions: The study demonstrated that the EF containing five HMOs supported normal growth, gastrointestinal (GI) tolerance and safe use in healthy term infants. 相似文献
62.
Wilson H. Steele Susan Wallace Boobis Michael R. Moore Abraham Goldberg Martin J. Brodie David J. Sumner 《European journal of clinical pharmacology》1978,13(4):309-313
Summary (1) Plasma protein binding of salicylate was studied in 14 patients with cutaneous hepatic porphyria (CHP) and 11 normal subjects using ultrafiltration with centrifugation (membrane cones) and continuous ultrafiltration. (2) Albumin and haemoglobin levels were significantly reduced in patients with CHP, and salicylate binding by ultrafiltration/centrifugation was 65% compared with 84% in normal subjects. (3) Plasma porphyrin levels were raised, but did not correlate with salicylate binding, and protoporphyrin or uroporphyrin added to plasma did not alter the amount of drug bound. (4) Palmitate added to plasma reduced salicylate binding by 9 to 20% but a crossover of patient and normal plasma proteins and ultrafiltrates confirmed that no other ultrafiltrable metabolites present in patient plasma appeared to cause decreased binding. (5) Scatchard plots obtained by continuous ultrafiltration for normal and patient plasma showed a reduction in the number of primary and secondary binding sites and an increase in the intrinsic association constants for both these sites. (6) It was concluded that the decreased salicylate binding in CHP was due to a reduced albumin concentration and altered salicylate albumin interaction. 相似文献
63.
W. H. Steele J. R. Lawrence J. F. B. Stuart C. A. McNeill 《European journal of clinical pharmacology》1979,15(5):363-366
Summary The protein binding of methotrexate by serum from eight normal volunteers was assessed by continuous ultrafiltration at pH 7.4 and 37°C. Methotrexate concentrations were measured by radioimmunoassay and the data analysed by the method of Scatchard. The major binding protein was albumin which bound 87.3% of the drug in serum. Analysis of the Scatchard plots indicated two distinct groups of binding sites. Class I was found to have 0.16±0.05 (S D) binding sites with an intrinsic association constant of 71.15±35.98 (S D)×104 M–1: Class II had 2.01±0.93 (S D) binding sites and an affinity of 0.18±0.15×104 M–1. No great change in the percentage of methotrexate bound occurred until the total concentration of the drug exceeded 50 µMol 1–1. 相似文献
64.
1. Studies have been made of the behavior of renal blood flow after partial constriction of the renal artery in twenty-four dogs. 2. When reduction in renal blood flow is produced by partial constriction of the renal artery, a readjustment of flow in the direction of normal occurs within a few minutes, subsequent constriction being again followed by a return of flow toward normal until the artery is markedly constricted. 3. Renal blood flow after marked constriction of the artery becomes extremely susceptible to the vasoconstrictive action of small doses of adrenalin, and flow may cease with larger doses for a considerable period of time. 4. Arterial hypertension of significant degree may follow partial constriction of one renal artery during brief experiments when adrenalin in addition has been administered. 5. Further evidence is presented in favor of the concept that the renal circulation enjoys a control independent of systemic arterial pressure. 相似文献
65.
M. Khair ElZarrad Aaron Y. Lee Rose Purcell Scott J. Steele 《CTS Clinical and Translational Science》2022,15(6):1332
Technological advancements are dramatically changing the landscape of therapeutic development. The convergence of advances in computing power, analytical methods, artificial intelligence, novel digital health tools, and cloud‐based platforms has the potential to power an exponential acceleration of evidence generation. For regulatory agencies responsible for evidence evaluation and oversight of medical products, these advances present both promises and challenges. Ultimately, realizing the translation and impact of these innovations that could potentially enhance therapeutic development and improve the health of individuals and the public will require a nimble and responsive regulatory approach. Supporting an adaptive policy‐making infrastructure that is poised to address novel regulatory considerations, creating a workforce to ensure relevant expertise, and fostering more diverse collaborations with a broader group of stakeholders are steps toward the goal of modernizing the regulatory ecosystem. This article outlines approaches that can help provide the flexibility and tools needed to foster innovation, while ensuring the safety and effectiveness of medical products. 相似文献
66.
67.
We have studied the effects of sulfasalazine and its metabolites on cell-mediated cytotoxicity by peripheral blood and intestinal mononuclear cells from both control and inflammatory bowel disease (IBD) patients. Sulfasalazine and sulfapyridine, as well as hydrocortisone and nordihydroguaiaretic acid inhibited spontaneous cell-mediated cytotoxicity by control and IBD peripheral blood cells. Sulfasalazine and nordihydroguaiaretic acid inhibited spontaneous cell-mediated cytotoxicity by control and IBD intestinal mononuclear cells cultured for 72 h in media alone. In contrast, 5-aminosalicylate, indomethacin and benzylimidazole had no effect on cytotoxicity by any cell population. Lectin-induced, antibody-dependent and interleukin-2-induced cell-mediated cytotoxicity, as well as lymphokine-activated killing were not inhibited by the drugs: inhibitory effects in these assays were primarily upon the underlying spontaneous cell-mediated cytotoxicity. The inhibition induced by sulfasalazine, sulfapyridine and nordihydroguaiaretic acid could not be reversed by adding the lipoxygenase metabolites leukotriene B4 or 12-hydroxyeicosatetraenoic acid. These findings demonstrate that spontaneous cell-mediated cytotoxicity by control and IBD mononuclear cells can be inhibited by sulfasalazine. 相似文献
68.
Allen C. Steere Stephen E. Malawista David R. Snydman Robert E. Shope Warren A. Andiman Martin R. Ross Francis M. Steele 《Arthritis \u0026amp; Rheumatology》1977,20(1):7-17
An epidemic form of arthritis has been occurring in eastern Connecticut at least since 1972, with the peak incidence of new cases in the summer and early fall. Its identification has been possible because of tight geographic clustering in some areas, and because of a characteristic preceding skin lesion in some patients. The authors studied 51 residents of three contiguous Connecticut communities—39 children and 12 adults—who developed an illness characterized by recurrent attacks of asymmetric swelling and pain in a few large joints, especially the knee. Attacks were usually short (median: 1 week) with much longer intervening periods of complete remission (median: 2.5 months), but some attacks lasted for months. To date the typical patient has had three recurrences, but 16 patients have had none. A median of 4 weeks (range: 1–24) before the onset of arthritis, 13 patients (25%) noted an erythematous papule that developed into an expanding, red, annular lesion, as much as 50 cm in diameter. Only 2 of 159 family members of patients had such a lesion and did not develop arthritis (P < 0.000001). The overall prevalence of the arthritis was 4.3 cases per 1,000 residents, but the prevalence among children living on four roads was 1 in 10. Six families had more than 1 affected member. Nine of 20 symptomatic patients had low serum C3 levels, compared to none of 31 asymptomatic patients (P < 0.005); no patient had iridocyclitis or a positive test for antinuclear antibodies. Neither cultures of synovium and synovial fluid nor serologic tests were positive for agents known to cause arthritis. “Lyme arthritis” is thought to be a previously unrecognized clinical entity, the epidemiology of which suggests transmission by an arthropod vector. 相似文献
69.
Summary The in vivo bending rigidity and bone mineral content of monkey ulnae and tibiae were measured. Bending rigidity in the anteroposterior
plane was measured by an impedance probe technique. Forced vibrations of the bones were induced with an electromechanical
shaker, and force and velocity at the driving point were determined. The responses over the range of 100–250 Hz were utilized
to compute the bending rigidity. Bone mineral content in the cross section was determined by a photon absorption technique.
Seventeen male monkeys (Macaca nemestrina) weighing 6–14 kg were evaluated. Repeatability of the rigidity measures was 4%. Bone mineral content was measured with a
precision of 3.5%. Bending rigidity was correlated with the mineral content of the cross section,r=0.899. Two monkeys were evaluated during prolonged hypodynamic restraint. Restraint produced regional losses of bone most
obviously in the proximal tibia. Local bone mineral content declines 17 to 24% and the average bending rigidity declines 12
to 22%. Changes in bones leading to a reduction in mineral content and stiffness are discussed. 相似文献
70.
G Steele S Sonis P Stelos R Rittgers N Zamcheck D Finn J Maltz R Mayer J Lokich R E Wilson 《Surgery》1978,83(6):648-654
Sixty-nine patients have been followed prospectively after curative resection of Dukes-Kirklin B-2 or C colorectal cancer. Serial plasma samples were studied in selected patients to determine changes in circulating immune complex concentrations (CIC) following primary tumor resection, and to compare serial plasma CIC and carcinoembryonic antigen (CEA) levels. CIC was determined in an average of seven serial samples per patient by inhibition of antibody-dependent cell-mediated cytotoxicity (ADCC). CEA assays were performed by the Hanson Z-gel method. Two distinct patterns of serial CIC have emerged. In seven patients with no known tumor recurrences, serial CEA levels and CIC oscillated regularly and were inversely related. In seven of eight patients whose tumors recurred, both CEA and CIC rose together. In three patients with elevated plasma CEA levels due to inflammatory bowel disease, serial Ag-Ab complex concentrations did not vary, nor did separated Ag or Ab fractions inhibit ADCC. These data suggest that, in patients following curative resection of colorectal cancer, serial changes in circulating immune complexes may discriminate between transient CEA elevations which occur despite no known tumor recurrence and tumor recurrence which is beyond the capacity of adequate host antitumor defense. 相似文献