Polyamines In Patients Research Articles

Metabolomic profile in patients with primary warm autoimmune haemolytic anaemia.

Autoimmune haemolytic anaemia (AIHA) is a rare clinical condition with immunoglobulin fixation on the surface of erythrocytes, with or without complement activation. The pathophysiology of AIHA is complex and multifactorial, presenting functional abnormalities of T and B lymphocytes that generate an imbalance between lymphocyte activation, immunotolerance and cytokine production that culminates in autoimmune haemolysis. In AIHA, further laboratory data are needed to predict relapse and refractoriness of therapy, and thus, prevent adverse side-effects and treatment-induced toxicity. The metabolomic profile of AIHA has not yet been described. Our group developed a cross-sectional study with follow-up to assess the metabolomic profile in these patients, as well as to compare the metabolites found depending on the activity and intensity of haemolysis. We analysed the plasma of 26 patients with primary warm AIHA compared to 150 healthy individuals by mass spectrometry. Of the 95 metabolites found in the patients with AIHA, four acylcarnitines, two phosphatidylcholines (PC), asymmetric dimethylarginine (ADMA) and three sphingomyelins were significantly increased. There was an increase in PC, spermine and spermidine in the AIHA group with haemolytic activity. The PC ae 34:3/PC ae 40:2 ratio, seen only in the 12-month relapse group, was a predictor of relapse with 81% specificity and 100% sensitivity. Increased sphingomyelin, ADMA, PC and polyamines in patients with warm AIHA can interfere in autoantigen and autoimmune recognition mechanisms in a number of ways (deficient action of regulatory T lymphocytes on erythrocyte recognition as self, negative regulation of macrophage nuclear factor kappa beta activity, perpetuation of effector T lymphocyte and antibody production against erythrocyte antigens). The presence of PC ae 34:3/PC ae 40:2 ratio as a relapse predictor can help in identifying cases that require more frequent follow-up or early second-line therapies.

The Potential Role of Polyamines in Epilepsy and Epilepsy-Related Pathophysiological Changes.

Epilepsy is one of the most common neurological disorders and severely impacts the life quality of patients. Polyamines are ubiquitous, positively charged aliphatic amines that are present at a relatively high level and help regulate the maintenance of cell membrane excitability and neuronal physiological functions in the central nervous system. Studies have shown abnormalities in the synthesis and catabolism of polyamines in patients with epilepsy and in animal models of epilepsy. The polyamine system seems to involve in the pathophysiological processes of epilepsy via several mechanisms such as the regulation of ion permeability via interaction with ion channels, involvement in antioxidation as hydroperoxide scavengers, and the induction of cell damage via the production of toxic metabolites. In this review, we try to describe the possible associations between polyamines and epilepsy and speculate that the polyamine system is a potential target for the development of novel strategies for epilepsy treatment.

Polyamines and cancer; The role of diet polyamines in patients with cancer

Polyamines (putrescine, spermidine and spermine) are basic compounds that are found in all living systems. They are responsible for cell proliferation and differentiation, DNA, RNA and protein synthesis. In addition to the endogenous synthesis of polyamines inside the cell, exogenous intake is also possible. The activity of enzymes that are involved in polyamine synthesis increases in cancer tissues, and consequently the level of polyamines rise. Therefore, polyamine concentrations in serum and urine of cancer patients are found in high levels. Reducing polyamine dietary intake has been shown to be beneficial on the quality of life in cancer patients. The aim of this review is to explain the functions of polyamines in cancer and the importance of low dietary intake of polyamines on cancer development and the treatment of patients and to summarize the literature.

433 Serum Polyamines in Patients With Non-Hodgkin's Lymphoma

433 Serum Polyamines in Patients With Non-Hodgkin's Lymphoma

口腔領域悪性腫瘍患者における尿中ポリアミンの検討

口腔領域悪性腫瘍患者における尿中ポリアミンの検討

Urinary excretion of polyamines in patients with surgical and accidental trauma: Effect of total parenteral nutrition

Excretion of polyamines first increases and then decreases in patients with multiple trauma receiving total parenteral nutrition (TPN). To separate the effects of trauma and TPN on polyamine excretion, we studied 12 patients with multiple trauma and 14 patients after surgery for colorectal malignancy. Patients were randomized to receive either TPN or hypocaloric glucose infusion. Urinary excretion of total and free polyamines, putrescine (PU), spermidine (SPD), and spermine (SP), and their metabolites, N 1-acetylspermidine (N 1-AcSPD) and N 8-acetylspermidine (N 8-AcSPD), and energy and nitrogen balance were measured. Polyamine excretion, excluding SP, markedly increased after trauma and surgery, exceeding the normal values by twofold to 10-fold. In patients receiving TPN, the excretion of total polyamines was 48% higher ( P < .01), PU was 34% higher ( P < .05), SPD was 35% higher ( P < .05), and SP was 350% higher ( P < .05) than in patients receiving hypocaloric glucose. Urinary excretion of SP was only 17% of the reference value during hypocaloric glucose ( P < .05), but was normal during TPN. The difference in polyamine excretion between nutrition groups was more pronounced when normalized for nitrogen or energy balance. Patients receiving TPN were more hypermetabolic than patients receiving hypocaloric glucose (resting energy expenditure, 1.36 ± 0.06 [SE] and 1.16 ± 0.04 times predicted values, respectively; P < .025). Statistically, energy expenditure could explain the difference in polyamine excretion between nutrition groups. Excretion of N 1-AcSPD was 116% higher ( P < .001), N 8-AcSPD was 72% higher ( P < .01), and total SPD was 123% higher ( P < .001) in patients with multiple trauma than in patients who had undergone elective surgery, and the difference in N 1-AcSPD and N 8-AcSPD could be explained by differences in nitrogen and energy balance between patient groups. In conclusion, TPN enhanced the already increased polyamine excretion in posttrauma and postsurgical patients. Excretion of N 1-AcSPD and N 8-AcSPD reflected the catabolic response to injury within each nutrition group. Our results suggest that urinary excretion of polyamines reflects metabolic activity in general rather than a solitary effect of a specific disease or therapy.

Urinary polyamines in patients with advanced cervical cancer or pelvic cancer recurrence during and after radiotherapy.

The urinary excretion of polyamines was evaluated before, during and after radiotherapy in 16 patients with advanced squamous cell carcinoma of the uterine cervix (stage IIb or IIIb) and in 7 cases with pelvic recurrence after surgery for various types of carcinoma. The concentration of spermidine was significantly higher in the patients with primary tumors than in those with recurrent tumors. After the first radiation fractions putrescine increased in the patients with primary tumors whereas it decreased in patients with recurrent tumors. The values tended to return to baseline levels with time following treatment initiation. Polyamine increased markedly during treatment in patients who remained disease-free for at least 5 years but not in the patients with progressive disease or relapse. The results suggest a different polyamine metabolism and a different response to radiotherapy of recurrent tumors compared to primary tumors. The increase of urinary polyamines, but not the baseline values, seemed to be correlated to the response after radiotherapy.

Decreased Urinary Polyamines in Patients with Psoriasis Treated with Etretinate

Oral administration of the aromatic retinoid etretinate is effective therapy for psoriasis and other epidermal hyperproliferative disorders. Since polyamine metabolism is known to be important in cell growth and differentiation, we measured urinary levels of the polyamines putrescine, spermidine, and spermine as a reflection of cutaneous polyamine metabolism in 19 psoriatic patients treated with etretinate for 16 weeks. Using thin-layer chromatography, polyamine determinations were performed on urine collected pretherapy, during therapy, and 8 weeks after therapy was concluded. Good to excellent clearing of psoriasis occurred in 18 of 19 patients. All urinary polyamines showed a downward trend in the first week of therapy, prior to significant clinical improvement. At week 16 of therapy, the greatest reduction in mean urinary polyamine content occurred. Mean putrescine levels decreased from pretherapy to week 16 by 27% (p less than 0.001), mean spermidine values fell by 34% (p less than 0.001), and mean spermine levels declined by 37% (p = 0.005). These data are consistent with the hypothesis that etretinate inhibits polyamine biosynthesis.

Determination of free and total polyamines in human serum and urine by ion-pairing high-performance liquid chromatography using a radial compression module : Application to blood polyamine determination in cancer patients treated or not treated with an ornithine decarboxylase inhibitor

A sensitive and rapid determination of free and total polyamines (putrescine, cadaverine, spermidine and spermine) in urine and serum is described. The procedure is based on reversed-phase high-performance liquid chromatographic separation using radial compression module (Radialpak C 8). The samples are purified with a silica gel Sep-Pak cartridge. The polyamines are converted to dansyl chloride derivatives and separated using a linear gradient of triethylammonium phosphate—methanol within 15 min. The lower limits of detection are 10 pmoles for spermine and 5 pmoles for other polyamines. This method is applied to cancer patients treated by cytotoxic chemotherapy with or without difluoromethylornithine (DFMO). All four polyamines are significantly increased in these patients before treatment. On day 8, after onset of treatment, the levels of polyamines in patients not treated with DFMO are more elevated than on day 1, while in patients treated with DFMO the levels are decreased. However, DFMO does not seem to modify the treatment result. The patients which have a low level of putrescine before and during treatment, do not respond to treatment. Perhaps this low level is the consequence of conjugation of this polyamine?

Cutaneous polyamines in psoriasis.

The polyamines putrescine, spermidine and spermine are intimately associated with cellular growth and division. Previous studies of the polyamines and their rate limiting biosynthetic enzyme, ornithine decarboxylase, in psoriasis have shown significant changes compared with non-psoriatic skin. We have further studied cutaneous polyamines in patients with psoriasis and in normal subjects, epidermal shave biopsies were taken and assayed for ornithine decarboxylase activity and polyamine levels. Psoriasis lesions showed increased ornithine decarboxylase activity compared with uninvolved skin. The levels of ornithine decarboxylase activity in uninvolved psoriasis skin were also higher than in normals. There was increased putrescine in involved psoriasis compared with uninvolved and normal skin. Spermidine and spermine were increased in psoriasis skin and in uninvolved skin and compared with normals. The spermidine/spermine ratio was greatest in involved skin compared with uninvolved and normal. These results confirm abnormal polyamine metabolism in both the involved and uninvolved skin of psoriatics.

Preliminary longitudinal studies of serum polyamines in patients with colorectal carcinoma

Polyamines, whose biosynthesis is a prerequisite for cell proliferation, are potential indicators of malignant growth. In view of this, serum polyamine levels were examined in longitudinal studies of patients with either colorectal carcinoma or Gardner's syndrome (inherited colonic polyposis possessing a potential for malignant degeneration). Of 10 patients examined longer than one year, serum polyamine levels reflected the disease status. This study indicates that biochemical surveillance of patients by polyamine analysis may be feasible and possibly applicable to other types of tumors.

Blood levels of polyamines in patients with brain tumor: special reference to relationship between blood levels of polyamines and histological finding, extension as well as treatment of tumor;.

In 38 patients with brain tumor and 17 controls, the blood levels of polyamines were measured, and studies were made on the relationship between these levels and varieties of tumors. In the group of 21 patients with glioma, these levels were significantly higher than those in the control (p<0.01), and in 14 out of 21 patients (67%) the levels exceeded the upper limit of normal range. In one patient with reticulum cell sarcoma, these levels were remarkably high. In the group of 4 patients with metastatic brain tumor, these levels were significantly higher than those in the control (p<0.05), and in 2 of 4 patients the levels exceeded the upper limit of normal range. The levels were all within normal range in 4 patients with neurinoma, 3 patients with meningioma, 2 patients with pituitary adenoma, 1 patient with pinealoma, and 1 patient with cerebellar hemangioblastoma. In 18 patients with glioma, studies were also made on the relationship between the blood levels of polyamines and the degree of histological malignancy and of extension of tumor. There was no significant difference in these levels between the control and the group of astrocytoma localized within a lobe, but the levels were significantly higher in the group of astrocytoma extending more widely and in the groups of anaplastic glioma or glioblastoma multiforme regardless of their size. In patients with glioma, the blood levels of polyamines before and after treatment were compared. In 3 patients subjected to surgical excision, irradiation and chemotherapy these levels were all within normal range after treatment, but in a case treated by irradiation and chemotherapy the values increased immediately after treatment.

Polyamines as predictors of success and failure in cancer chemotherapy

Polyamines appear to have clinical utility for monitoring cancer therapy. Investigations on the patterns of urinary excretion of polyamines in patients receiving cancer chemotherapy and studies of the tritiated-thymidine labelling index of tumour cells in a subgroup of these patients form the basis for a hypothesis that spermidine can serve as a marker of tumour-cell kill, whereas putrescine appears to reflect the proliferative behaviour or "growth fraction" of the tumour. Although tests of this hypothesis are necessary to establish the predictive value of polyamines for monitoring cancer therapy, it is clear that polyamines may provide important new information on tumour cytokinetic parameters.