scholarly journals The Bluegreen Algae (AFA) Consumption over 48 h Increases the Total Number of Peripheral CD34+ Cells in Healthy Patients: Effect of Short-Term and Long-Term Nutritional Supplementation (Curcumin/AFA) on CD34+ Levels (Blood)

2020 ◽  
Vol 10 (2) ◽  
pp. 49
Author(s):  
José Joaquín Merino ◽  
María Eugenia Cabaña-Muñoz ◽  
María Jesús Pelaz

Several active principles from plants could trigger the release of stem cells from the bone marrow. Stem cell mobilizers have shown side effects in patients. Thus, the purpose of this paper is to find the natural products from plants (curcuminoids, glycosinolate of sulforaphane, AFA bluegreen algae), which could be potential stem mobilizes without adverse side effects. The antioxidant curcumin [1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-2,5-dione], glycosinolate of sulforaphane (broccoli) or AFA (Aphanizomenon flos) extract promote beneficial effects in patients. The number of circulating stem cells were monitored by HSC marker-CD34 by flow cytometry in peripheral blood from healthy subjects. CD34 is a hematological stem cells (HSC) marker. A double-blind study was conducted in 22 healthy subjects. We have evaluated whether short-term AFA—Aphanizomenon flos aquae—algae or curcuminoids consumption (powder or liquid formulation) over 48 consecutive hours could increase the total number of peripheral CD34+ blood cells (n = 22, n = 5 subjects/group). The total number of circulating CD34+ cells were quantified after short-term and long-term nutritional supplementation; their levels were compared with their own basal levels (n = 5/group, controls: before taking any supplement) or placebo-treated patients (n = 7); their average age was 54 years old. We also evaluated whether long-term nutritional supplementation with several nutraceuticals could enhance HSC mobilization by increasing the total number of peripheral CD-34+ cell after seven or 38 consecutive days of administration (n = 5, with seven placebo-treated patients). The long-term administration take place with these doses/day [curcuminoids: 2000 mg/day, equivalent to 120 mg of curcuminoids/day), glycosinolate of sulforaphane (66 mg/day), plus AFA Algae bluegreen extract (400 mg/day)]. On the last day (10 a.m.) of treatment, blood samples were collected six hours after taking these supplements; the average age was 54 years old. Notably, the blue green AFA algae extract consumption over 48 h enhances HSC mobilization by increasing the total number of peripheral CD34+ cells. The long-term administration with curcuminoids, glycosinolate of sulforaphane, and AFA bluegreen algae extract also increased the total number of CD34-HSC cells after seven or 38 days of consecutive of administration in healthy subjects.

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4390-4390 ◽  
Author(s):  
Abhinav Deol ◽  
Judith Abrams ◽  
Ashiq Masood ◽  
Zaid Al-Kadhimi ◽  
Muneer H. Abidi ◽  
...  

Abstract Abstract 4390 Background: Plerixafor is a CXCR 4 antagonist which is now approved for use for stem cell (SC) mobilization with granulocyte colony stimulating factor (GCSF) in patients with non Hodgkin lymphoma (NHL) or multiple myeloma (MM). Prior to the approval of plerixafor, we enrolled 49 patients in a compassionate use protocol at our institution to mobilize SC for patients who previously failed at least one mobilization attempt. Methods: Patients received 0.24 mg/kg of plerixafor subcutaneously 9 –11 hrs prior to apheresis in addition to twice daily GCSF. Results: Median age of the patients was 64 years (range, 23–74 years). NHL was the most common diagnosis in 27 (55%) patients, followed by MM with 17(35%) patients and HD with 5 (10%) patients. Thirty nine patients (80%) had been treated with more than 2 chemotherapeutic regimens prior to the first attempt at stem cell collection. Thirty seven patients (76%) failed one previous mobilization attempt, while 12 (24%) had failed 2 or more previous attempts. Using the combination of Plerixafor and GCSF we collected ≥ 2.5 × 106 CD34+ cells/Kg in 33 patients (67%). The median days for pheresis were 1 day with a range of 1 to 3 days. The median SC dose collected was 4 × 106 CD34+ cells/Kg, with a range 2.5 – 14.3. The median CD-34+ peripheral blood count on the 1st day of their collection with plerixafor was 22.4/uL. In contrast the median peripheral blood CD-34+ cell count in these patients on the day of their first collection which failed was 6.2 /uL. The median increase using G-CSF and plerixafor was 14.9 CD-34+ cells/uL. We collected ≥ 2.5 × 106 CD34+ cells/Kg on 4/5 (80%) patients with HD, 13/17 (76%) patients with MM and 16/27 (59%) patients with NHL. Sixteen patients (33%) collected < 2.5 × 106 CD34+ cells/Kg. The median cell dose collected in these patients was 1.4 × 106 CD34+ cells/Kg with a range, 0.4–2.2. The median number of days of pheresis was 2 days (range, 1–4 days). In these16 patients the median CD-34+ count on the day of their previous failed collection was11.2/uL. Their CD-34+ cell count on their first day of collection after the use of G-CSF and plerixafor was 8.3/ul. Figure 1 shows the change in peripheral CD34 counts with the prior mobilization attempt and after plerixafor mobilization, for 38 patients in whom data was available. The most common side effects attributed to plerixafor were diarrhea, fatigue, thrombocytopenia and bone pain; observed in 12%, 8%, 8% and 6% patients, respectively. Forty three of the 49 patients proceeded to an autologus peripheral blood SC transplant, 34 patients received ≥ 2.5 × 106 CD34+ cells/Kg. Thirty two of these patients used the plerixafor collection as the only source of SC. Two patients had their plerixafor mobilized SC combined with a previous suboptimal SC collection. Nine patients received < 2.5 × 106 CD34 + cells/Kg; 4 patients received plerixafor mobilized SC alone, 5 patients received plerixafor mobilized SC combined with their previously mobilized SC. The preparative regimens used were R- BEAM (20 patients), Melphalan (16 patients), BEAM (6 patients) and Etoposide+TBI (1 patient). All patients received GCSF from day +6 till WBC engraftment. The median days of WBC and platelet engraftment were day +11 (range, 9–13 days) and day +16 (range, 11–77 days), respectively. There was no significant difference in days to engraftment between the patients who collected greater or less than 2.5 × 106 CD34 + cells/Kg. With a median follow up 13.7 months, long term engraftment data is available on 27 patients. The median white cell count, hemoglobin and platelet count 1 year after transplant was 4.7 × 109/L, 12.2 g/dL and 109 ×109/L, respectively. There was no significant difference in counts at the 1 year mark between patients who collected more or less than 2.5 × 106 CD34 + cells/Kg. To date 15 patients have evidence of disease progression. Two patients have developed MDS/AML post transplant. Conclusion: Overall, plerixafor leads to mobilization of sufficient stem cells in a vast majority of patients who have failed previous mobilization attempts and allows more patients to proceed to an autologous SC transplant. Plerixafor is well tolerated with minimal side effects, acceptable time to engraftment and acceptable peripheral blood counts at 1 yr after the transplant. Our analysis suggests that failure to increase peripheral CD34 count after plerixafor when compared to previous attempts may predict unsuccessful mobilization. Disclosures: Lum: Transtarget Inc: Equity Ownership, Founder of Transtarget.


Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3383-3383 ◽  
Author(s):  
Jeff Tauer ◽  
Leonard Shultz ◽  
Tessa Holyoake ◽  
Ravi Bhatia

Abstract The NOD/SCID mouse model has been widely used to assay human hematopoietic cells capable of long-term multilineage engraftment (SCID-repopulating cells or SRC). Leukemia cells from CML patients can also engraft in NOD-SCID mice. However the utility of this model for studying CML stem cells is limited by inconsistent and low levels of engraftment, and lack of a leukemia-related phenotype of engrafted cells. Since NOD/SCID IL2Rγchain KO (NOG) mice support superior engraftment of human hematopoietic cells compared with NOD/SCID mice, they may allow for improved evaluation of CML stem cells. In the current study we investigated engraftment of CML CD34+ cells in the NOG mouse model. CD34+ cells were transplanted into irradiated (300 cGy) 8 wks old NOG mice via tail vein injection. Blood samples were obtained at 4 wks intervals to monitor human cell engraftment. At the end of the maintenance period of 16–18 wks, animals were euthanized and marrow content of femora, spleen cells and peripheral blood were obtained. Human cell engraftment was analyzed by flow cytometry after labeling cells with anti-human CD45 mAb and specific human cell subsets detected by staining with human CD34, CD33, CD14, CD11b, CD19 and CD3 mAbs. Establishment of human hematopoiesis was consistently seen 4 weeks after injection. Larger numbers of CML (1–2 x106) compared to normal bone marrow (1–8x105) CD34+ cells were required to establish engraftment, which is consistent with previous reports. Interestingly CML CD34+ cells established their highest levels of engraftment in blood 4 wks after transplantation (14.9±5.9% CD45+ cells, n=13) and engraftment levels were significantly lower at 8 wks (1.8±0.3%) and beyond. However engraftment was consistently detected in blood up to 16–20 wks. The engraftment kinetics of CML cells was strikingly different from that of normal CD34+ cells which while showing similar levels of engraftment at 4 wks (12.6±3.8%, n=16), showed considerably higher engraftment at 8 wks (19.2±3.8%) with a gradual decline subsequently (11.5±2.7% at 12 wks). Analysis after autopsy at 16–18 wks revealed higher levels of human cell engraftment in mouse BM and spleen compared with blood. CML CD34+ cells showed reduced BM engraftment compared with normal CD34+ cells (7.3±4.8% vs. 22.1±9.0% CD45+ cells, n=7, p<0.01). CML CD34+ cells engrafted with myeloid lineage cells and minimal lymphoid engraftment was seen (CD33: 5.2±3.7%, CD11b: 2.6±1.6% and CD19: 0.1±0.1%), whereas normal CD34+ cells engrafted with both myeloid and lymphoid cells (CD33: 7±3%, CD11b: 1.6±0.6% and CD19: 11±4.3%). We also observed reduced frequency of CD34+ cells in mice receiving CML compared with normal cells (2.6±2.5% vs. 6.2±3.0%, p<0.05). In conclusion we show, using an improved mouse model of human hematopoiesis, that CML SRC have similar short-term but reduced long-term engraftment capacity compared with normal SRC, possibly indicating a preponderance of short-term repopulating cells or increased HSC turnover. CML SRC demonstrated predominantly myeloid differentiation compared with balanced myeloid and lymphoid engraftment of normal SRC. These results support the utility of the NOG mouse model to investigate functional characteristics of CML stem cells and study the activity of specific therapeutic interventions against primitive CML cells.


Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4129-4129
Author(s):  
Ioannis Kotsianidis ◽  
Scott Patterson ◽  
Marianna Politou ◽  
Antonio Almeida ◽  
Despoina Pantelidou ◽  
...  

Abstract NKT cells, a novel class of regulatory T cells, secrete haemopoietic cytokines (GM-CSF, IL-3, IL-6) upon engagement of their TCR. Because of this property we hypothesized that NKT cells are involved in the regulation of haemopoiesis. NKT cells constitute &lt;0.1% of T cells in blood, bone marrow and cord blood and are restricted by the glycolipid-presenting, non-polymorphic MHC-like molecule CD1d. CD1d is expressed in antigen presenting cells, thymocytes and in a variety of epithelial tissues including keratinocytes and enterocytes, but its expression in haematopoietic stem cells (HSC) has not been studied. Therefore we studied first the expression and function of CD1d in haemopoietic stem cells. Using multi-colour flow cytometry, we show that 1% of MACS-selected cord blood CD34+ cells are CD1d+ (n=6, range 0.4–1.67%). CD1d+CD34+ HSC express a variety of surface markers indicative of primitive HSC: CD7: 36.1% (35.6–36.4%), CD133: 68% (46.2–81.54%), CD117:74.2% (51–85.5%) and CD90 (Thy-1): 32.3% (26.7–39.1%); moreover, 6,2% (1.9–10.5%) and 12,8% (10.1–16%) of CD1d+CD34+ are CD1d+CD34+HLADR− and CD1d+CD34+CD38− respectively, consistent with an immature HSC phenotype. Expression of these markers by CD1d−CD34+ were identical to CD1d+CD34+ cells. Consistent with this, in long-term colony initiating cell (LTC-IC) assays (n=4), highly purified, flow-sorted, lineage-depleted (Stem Cell Technologies) Lin-CD1d+CD34+ HSC displayed a LTC-IC frequency of 1 in 35.7 cells (range 24.4–38) equivalent to those of CD1d−CD34+ HSC: LTC-IC frequency of 1 in 25.4 cells (range 20–30.3). Short term CFC activity of Lin−CD34+CD1d+ is slightly lower than their Lin−CD1d−CD34+ counterparts: 1 CFC per 15.3 cells (7.7–37.7) versus 1 CFC per 4.2 cells (3.8–5), respectively. To investigate the effect of cord blood NKT cells on the CFC activity of CD34+ cells, NKT were first activated ex vivo for 10 days in the presence of the CD1d-presented glycolipid a-galactosylceramide and subsequently were purified by flow-sorting using mAbs specific to their TCR a and b chains, i.e., anti-TCR Va24 and Vb11. Purified NKT were co-cultured in a ratio of 10:1 with CD34+ cells. In the absence of exogenous cytokines NKT enhanced the clonogenic capacity of CD34+ cells by 3-fold: 1 CFC per 14 cells (range 10.4–21) in the presence of NKT vs 1 per 43 cells (range 37–55.5) in the absence of NKT (n=4; p=0.024). By contrast, activated or resting autologous T cells co-cultured with CD34+ cells at the same ratio (10:1) had no effect on the CFC frequency, indicating that this enhancing effect on haemopoiesis is a unique property of NKT cells. The effect of NKT in the long-term clonogenic capacity is currently being evaluated. In summary, we have shown that a) CD1d is a novel marker expressed in HSC with long- and short -term clonogenic ability and b) CD1d-restricted NKT cells promote haemopoiesis These findings reveal a novel link between haemopoiesis and the CD1d-NKT axis of immune regulation and set the scene for the study of the role of NKT cells in the processes of engraftment and rejection in HSC transplantation.


2021 ◽  
Vol 30 ◽  
pp. 096368972110360
Author(s):  
Daniel Lysak ◽  
Michaela Brychtová ◽  
Martin Leba ◽  
Miroslava Čedíková ◽  
Daniel Georgiev ◽  
...  

Cryopreserved haematopoietic progenitor cells are used to restore autologous haematopoiesis after high dose chemotherapy. Although the cells are routinely stored for a long period, concerns remain about the maximum storage time and the possible negative effect of storage on their potency. We evaluated the effect of cryopreservation on the quality of peripheral stem cell grafts stored for a short (3 months) and a long (10 years) period and we compared it to native products.The viability of CD34+ cells remained unaffected during storage, the apoptotic cells were represented up to 10% and did not differ between groups. The clonogenic activity measured by ATP production has decreased with the length of storage (ATP/cell 1.28 nM in native vs. 0.63 in long term stored products, P < 0.05). Only borderline changes without statistical significance were detected when examining mitochondrial and aldehyde dehydrogenase metabolic activity and intracellular pH, showing their good preservation during cell storage. Our experience demonstrates that cryostorage has no major negative effect on stem cell quality and potency, and therefore autologous stem cells can be stored safely for an extended period of at least 10 years. On the other hand, long term storage for 10 years and longer may lead to mild reduction of clonogenic capacity. When a sufficient dose of stem cells is infused, these changes will not have a clinical impact. However, in products stored beyond 10 years, especially when a low number of CD34+ cells is available, the quality of stem cell graft should be verified before infusion using the appropriate potency assays.


2010 ◽  
Vol 2 ◽  
pp. CMT.S1168
Author(s):  
Francisco M. Abarca ◽  
Theodore J. Saclarides ◽  
Marc I. Brand

Objectives Review and summarize the mechanism of action of methylnaltrexone bromide (methylnaltrexone) and its effectiveness in the treatment of opioid-induced constipation. Data Source A multi-database search was conducted using PubMed and MEDLINE databases, in addition to electronic links to related articles and references. Background Opioids are effective medications for the management of moderate to severe pain, but they are associated with a number of side effects, especially within the gastrointestinal system. Constipation is a very common adverse reaction in patients with late-stage, adverse illness, who require long term administration of opioids on a chronic basis to help alleviate pain. In April 2008, the Food and Drug Administration approved the use of methylnaltrexone, a quaternary derivative of naltrexone which does not cross the blood brain barrier, for the management of patients with opioid-induced constipation. Methylnaltrexone acts as a selective peripheral Mu-receptor antagonist, without affecting the effects of opioids on central analgesia. Conclusions Studies have been shown that methylnaltrexone can be used safely in the treatment of opioid-induced constipation without either interfering with opioid effects on central anesthesia or precipitating opioid withdrawal.


1996 ◽  
Vol 7 ◽  
pp. 15-18
Author(s):  
W.E. Fibbe ◽  
J. Mark ◽  
J.M. Zijlmans ◽  
R. Willemze
Keyword(s):  

1992 ◽  
Vol 29 (6) ◽  
pp. 521-527 ◽  
Author(s):  
J. S. Cullor ◽  
W. Smith ◽  
J. G. Zinkl ◽  
J. D. Dellinger ◽  
T. Boone

Colony-stimulating factors are a category of glycoproteins that are instrumental in the regulation of hematopoiesis and inflammation. This investigation documented the clinical bone marrow and peripheral blood responses to short-term and long-term administration of a recombinant bovine granulocyte colony-stimulating factor (rb-GCSF) and an analog, where the cysteine at position 17 was substituted with a serine (rb-GCSF ser17). The colony-stimulating factors produced the expected changes in the hematologic findings of the bovine subjects in the study, and there was a cell-specific response to the compounds. The sustained neutrophilia in the long-term study indicates that the bovine species can tolerate the administration of recombinant forms of bovine GCSF for extended periods of time without detectable adverse side effects. The neutrophils from the short-term study revealed no apparent fluctuation, either as enhanced or reduced capability to reduce nitro blue tetrazolium as compared to pretreatment neutrophils. The administration of both recombinant forms of GCSF produced large increases in the bone marrow myeloid: erythroid (M:E) ratio concomitantly with the neutrophilias. This is the first preliminary report documenting the bone marrow response of cattle to the native and recombinant (rb-GCSF ser17) forms of bovine GCSF.


PEDIATRICS ◽  
1994 ◽  
Vol 94 (5) ◽  
pp. 724-731 ◽  
Author(s):  
Brigitta U. Mueller ◽  
Karina M. Butler ◽  
Vicki L. Stocker ◽  
Frank M. Balis ◽  
Philip A. Pizzo ◽  
...  

Background. Didanosine has demonstrated promising antiviral activity and a tolerable toxicity profile in short term studies. We describe a cohort of HIV-infected children who were treated for a prolonged period of time with didanosine. Methods. Children (6 months to 18 years of age) with symptomatic HIV infection or an absolute CD4 count &lt; 0.5 x 109 cells/L, received oral didanosine at doses between 20 mg/m2 to 180 mg/m2 every 8 hours. Clinical, immunological, and virological parameters were assessed at least every 2 months. The pharmacokinetics of didanosine were evaluated in 85 patients. Results. Previously untreated children (n = 51) and children who had received prior antiretroviral therapy (n = 52) were enrolled in the study (median time on study 22.6 months; range 2 to 48). The long-term administration of didanosine was well tolerated and no new toxicities were observed. The absolute CD4 count increased by ≥ .05 x 109 cells/L in 28 of 87 (32%) of patients after 6 months of therapy. Responses were also sustained in 41% of these children after 3 years of therapy. Children entering the study with a CD4 count &gt;0.1 x 109 cells/L (n = 51) had a marked survival advantage (P = .00002) with an estimated survival probability after 3 years of 80% compared to 39% for children with lower CD4 counts. Although the area under the curve of didanosine increased proportionally with the dose, there was considerable interpatient variability at each dose level. There was no apparent relationship between surrogate markers of clinical outcome and plasma drug concentration. Conclusions. Didanosine was well tolerated with chronic administration, and toxicities were uncommon and usually reversible. In 41% of patients, the CD4 count increased and was maintained at the higher level even after years of treatment.


2022 ◽  
pp. 269-288
Author(s):  
Ayesha Kanwal ◽  
Zeeshan Ahmad Bhutta ◽  
Ambreen Ashar ◽  
Ashar Mahfooz ◽  
Rizwan Ahmed ◽  
...  

Human mortality due to drug-resistant infections is becoming more prevalent in our society. Antibiotics are impotent due to abuse and/or misuse, leading to new, more expensive, and more effective medicines and treatments. Therefore, it causes many short-term and long-term side effects in the patient. On the other hand, nanoparticles have exhibited antibacterial activity against various pathogens due to their small size and ability to destroy cells by various mechanisms. Unlike antibiotics for the treatment of patients' diseases and infections, nanomaterials provide an exciting way to limit the growth of microorganisms due to infections in humans. This has led to the development of a number of nanoparticles as active antibacterial agents. Therefore, the authors have carefully reviewed the recent developments in the use of nanomaterials for antibacterial applications and the mechanisms that make them an effective alternate antibacterial agent.


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