Identification of methylated metabolites of oat avenanthramides in human plasma using UHPLC QToF-MS

Oat avenanthramides (AVAs) are a group of phenolic alkaloids, consisting of an anthranilic acid and a hydroxycinnamic acid linked by a pseudo-peptide bond. Bioavailability of AVA is poor in humans, suggesting transformations for rapid excretion. Thus, we aim to identify metabolites of AVA isomers in plasma of humans after consuming AVA-enriched oats. After lipid removal, AVA and their metabolites in plasma were extracted with ethyl acetate and analysed using an Agilent UHPLC-QToF-MS. Pharmacokinetics of AVA-O showed a bimodal distribution with C_max1 and 2 for AVA-O at 5.9?±?5.2 and 7.9?±?7.0?ng/mL and T_max1 and 2 at 1.7?±?0.7 and 3.1?±?1.2?h, respectively. Only the methyl-AVA-O showed a single C_max at 14?±?9.9?ng/mL AVA-O equivalents and a T_max of 2.4?±?2.7?h. This analysis is the first to identify methylated metabolites of AVAs and AVA aglycones in human blood after acute AVA consumption.     

Antibodies,boosters, and optimizing SARS-CoV-2 vaccines for transplantation: A call for more research

Despite emerging data suggesting reduced antibody responses among solid organ transplant recipients following SARS-CoV-2 vaccine, critical unanswered questions remain. The clinical implications of the reduced humoral response need to be assessed through prospective studies. Studies are likewise needed to inform which vaccine dosing strategies result in improved immunity and if such approaches maximize protection against severe infection in the vulnerable transplant population.     

Identification of a non-fluorescent isodicentric Y chromosome by molecular cytogenetic techniques

A 12 1/2-month-old girl was referred because of short stature, short neck, large internipple distance and simian crease on her right hand. By routine cytogenetic techniques the presence of an unidentifiable marker chromosome and loss of one X chromosome was noted (i.e. 45, X/46, X, mar/47, X, mar, +mar). By fluorescence in situ hybridization (FISH) technique, the marker chromosome was identified as an isodicentric non-fluorescent Y chromosome ((45, X/46, X, idic (Y^nf)/47, X, idic (Y^nf), +idic (Y^nf)). Although the clinical significance of this finding cannot be assessed at present, possible development of gonadoblastoma in such cases is a major concern and warrants follow-up evaluations.     

Neurotensin — macrophage interaction: Specific binding and augmentation of phagocytosis

Neurotensin (NT) was found to bind to thioglycollate-elicited mouse peritoneal macrophages and to modulate their phagocytic capability. A Scatchard analysis of the binding curve of [³H]NT suggests the presence of two subclasses of binding sites having a.−a K_D of 0.9 nM (4800 sites per cell) and b.−a K_D of 28 nM (33500 sites per cell). NT as well as two of its partial sequences, NT(8–13) and NT(6–13) competed with [³H]NT for its binding whereas NT(1–10) was rather ineffective. [³H]NT was also competitively displaced by tuftsin, substance P (SP) and by SP (1–4). The K_I values estimated for all the above competitive inhibitors of [³H]NT binding (except for NT) suggest interaction with the relatively low affinity sites.NT exerts a biphasic effect on the phagocytic response of macrophages. At a concentration range of 10⁻¹⁴–10⁻⁹ M NT had a dose dependent augmenting effect on the phagocytic response (up to 2 fold), further increase in concentration (>10⁻⁹M) of NT resulted in a gradual decrease of the augmented response which disappears at 10⁻⁷ M NT. NT(8–13), NT(6–13) as well as NT(1–10) augment the phagocytic response of macrophages. However the maximal effect with these peptides was attained at about 10⁻⁷ M and stayed at the same level at concentrations up to 10⁻⁵ M. The phagocytosis augmenting dose-response curves of these peptides resembled that of tuftsin and SP, two unrelated peptides.It is suggested that NT-phagocyte interaction may be of relevance in the regulation of the functions of phagocytic cells.     

Influence of 1,25 dihydroxycholecalciferol on sexual dysfunction and related endocrine parameters in patiens on maintenance hemodialysis

It has been postulated that hyperparahyroidism is in part responsible for sexual dysfunction in dialyzed patients and that this could improved by 1,25(Oh)2D3. In a single blind study patients on maintenance hemodialysis were treated after a control period with 1,25 (OH)2D3 and with placebo in random order. Sexual performance was assessed with a detailed semistructured psychiatric interview protocol in 14 and several endocrine parameters were analyzed in 15 patients. Under control conditions sexual function was disturbed in 11/14 patients. Plasma testosterone was moderately decreased in men, PRL and PTH levels were distinctly elevated in both sexes. 1,25(OH)2D3 raised serum calcium levels significantly from 9.6 to10.6 mg/100 ml ( P < 0.01) and lowered PTh from 1.39 to 0.82 ng/ml ( P < 0.01). However, no improvement in sexual function (such as libido, frequency of intercourse or masturbation) was found, and apart from a slight rise of testosterone in men and moderate fall of PRl in men and women endocrine parameters remained unchanged. It is concluded that in spite of an improvement of secondary hyperparathyroidism, treatment with 1,25(OH)2D3 for 2 to 4 months was of no value in improving sexual dysfunction in these hemodialysis patients.     

Association between transfusion of whole blood and recurrence of cancer

Transfusion affects the immune response to renal transplantation and may be associated with recurrence of various human neoplasms. Data from patients with colonic, rectal, cervical, and prostate tumours showed an association between transfusion of any amount of whole blood or larger amounts of red blood cells at the time of surgery and later recurrence of cancer. Recipients of one unit of whole blood had a significantly higher incidence of recurrence (45%) than recipients of a single unit of red cells (12%) (p = 0.03). Recipients of two units of whole blood also had a higher rate of recurrence (52%) than those receiving two units of red cells (23%) (p = 0.03). Recipients of any amount of whole blood had similar recurrence rates (38-52%). Recipients of four or more units of red blood cells had a higher rate of recurrence (55%) than those receiving three or fewer units of red blood cells (20%) (p = 0.005). Mortality due to cancer in patients receiving three or fewer units of red blood cells (2%) was similar to that in patients who did not have transfusions (7%) and significantly lower than that observed in patients receiving three or fewer units of whole blood (20%) (p = 0.003). A proportional hazards risk analysis showed that transfusion of any whole blood or more than three units of red blood cells was significantly associated with earlier recurrence and death due to cancer. These data support an association between transfusion and recurrence of cancer. They also suggest that some factor present in greater amounts in whole blood, such as plasma, may contribute to the increased risk of recurrence in patients who have undergone transfusion. Until the questions raised by retrospective studies of cancer recurrence and transfusion can be answered by prospective interventional trials with washed red blood cells, red blood cells should be transfused to patients with cancer in preference to whole blood when clinically feasible.     

Effect of microinjected catalytic fragment of protein kinase C on morphological change in Swiss 3T3 cells

Although phorbol esters can enhance formation of an active, catalytic domain of protein kinase C (PKC) in intact cells, little is known about the actual importance of the proteolytic pathway in mediating cellular responses to the phorbol esters or other PKC activators. To explore this issue, we examined the effect of microinjected catalytic fragment of PKC on Swiss 3T3 cell morphology. In contrast to the dramatic, rapid response upon phorbol ester treatment, catalytic fragment microinjected in the presence of bovine serum albumin or normal goat immunoglobulin G as carrier protein had no effect. A morphological response similar but not identical to the effect of phorbol ester treatment was obtained, however, if catalytic fragment was microinjected in the presence of normal rabbit immunoglobulin G rather than the usual carrier proteins. The normal rabbit immunoglobulin by itself was inactive. Although the mechanism remains undefined, normal rabbit immunoglobulin but not other carrier proteins modulated PKC activity in vitro. We conclude that the generation of free catalytic fragment of PKC cannot account for the morphological response of Swiss 3T3 cells to the phorbol esters; secondary factors may, however, potentiate its action.