The Long-term Outcome of Pediatric Kidney Transplantation in Iran: Results of a 25-year Single-Center Cohort Study.

BACKGROUND: Kidney transplantation is the optimal treatment for end-stage renal disease in children. However, long-term graft survival has not significantly improved among pediatric patients. OBJECTIVE: To investigate the determinants of long-term graft survival among Iranian pediatric recipients of kidney transplantation. METHODS: In a single-center cohort study, we studied 314 pediatric kidney transplantations performed from 1989 to 2013 at Dr. Shariati Hospital, Tehran, Iran. Different variables were collected for each patient and graft survival rates were calculated. RESULTS: After a mean±SD follow-up period of 15.8±4.0 years, the mean±SD graft survival rate was 14.5±0.5 years; the 1-, 5-, 10-, and 20-year mean graft survival rates were 90%, 81%, 62%, and 62%, respectively. The corresponding patient survival rates were 100%, 99.4%, 97.8%, and 96.5%, respectively. Pre-emptive transplantation (p=0.006), and living graft donation (p=0.002) led to higher graft survival, while acute rejection (p=0.002), and primary disease of primary hyperoxaluria (p=0.001) led to lower graft survival. Chronic rejection was the most frequent cause of graft loss. CONCLUSION: Short-term graft survival still outpaces the long-term outcome. Modifying the mentioned determinants, with more intense immunosuppression for greater prevention of acute and chronic rejection, and increased rate of pre-emptive transplantation and living donor transplantation, long-term graft survival may significantly improve in future.

Reliability of pre-transplant live donor renal biopsies in predicting the graft outcome.

BACKGROUND: Biopsy from deceased donors is of great value in predicting the efficacy and mid-term and long-term outcome of kidney transplantation. OBJECTIVE: To determine the prevalence of pathological changes in live donors' kidneys and their association with the graft outcome. METHODS: This cohort study was performed among a group of renal transplant recipients. Biopsy was taken from donor's kidney. The functionality of the grafted kidney was then evaluated by measuring serum creatinine, based on which, the patients were categorized into "successful" and "unsuccessful" groups. The results were compared based on biopsy results. RESULT: We studied 58 kidneys from live donors. The mean±SD urine volume on the first day after transplantation was 10,052±3286 mL. Absence of allograft dysfunction was seen in 55 (95%) patients during a month, 51 (88%) patients in 6 months, and 53 (91%) within a year. Glomerulosclerosis was seen in 20 (35%) patients, fibrosis in 9 (16%), tubular atrophy in 5 (9%), and intimal fibrosis in 3 (5%). The mean±SD serum creatinine in patients within 1-month survival was 1.15±0.19, within 3-month survival was 1.17±0.20, within 6-month survival was 1.21±0.20, within 9-month survival was 1.43±1.28, and within 1-year survival was 1.14±0.22. CONCLUSION: Kidney biopsy from live donors can show us a general status of kidney. Serum creatinine is the test of choice for evaluating the grafted kidney function.

Inhibition of protein glycation by essential oils of branchlets and fruits of Juniperus communis subsp. hemisphaerica.

Oxidative stress and protein glycation play pivotal roles in the pathophysiology of diabetes mellitus and its vascular complications. The present study aimed to investigate the anti-glycation properties of essential oils obtained from different parts of Juniperus communis subsp. hemisphaerica. The branchlets of male tree (BMT) and branchlets of female (BFT) tree, and fruits of J. communis subsp. hemisphaerica were extracted using steam distillation method. The oils were phytochemically analyzed using gas chromatography-mass spectrometry. Anti-glycation properties were evaluated using hemoglobin and insulin glycation assays. Overall, 18 volatile components were identified in the J. communis subsp. hemisphaerica oils, amounting to 82.1%, 100.0% and 96.4% of the BMT, BFT and fruit oils, respectively. Promising inhibitory activity was observed from all concentrations of the tested oils in the hemoglobin and insulin glycation assays. The inhibitory activities peaked to 89.9% (BFT oil; 200 µg mL(-1)) and 81.0% (BFT oil; 600 µg mL(-1)) in the hemoglobin and insulin glycation assays, respectively. The evidence from this study suggests that essential oils obtained from the fruits and branchlets of J. communis subsp. hemisphaerica possess anti-glycation properties. These activities may find implication for the prevention and treatment of diabetic complications.

Effect of some high consumption spices on hemoglobin glycation.

Formation of glycation products is major factor responsible in complications of diabetes. Worldwide trend is toward the use of natural additives in reducing the complications of diseases. Therefore, there is a growing interest in natural antiglycation found in plants. Herbs and spices are one of the most important targets to search for natural antiglycation from the point of view of safety. This study investigated the ability of some of the spices to inhibit glycation process in a hemoglobin/glucose model system and compared their potency with each other. For this subject the best concentration and time to incubate glucose with hemoglobin was investigated. Then the glycosylation degree of hemoglobin in the presence of extracts by the three concentrations 0.25, 0.5 and 1 µg/ml was measured colorimetrically at 520 nm. Results represent that some of extracts such as wild caraway, turmeric, cardamom and black pepper have inhibitory effects on hemoglobin glycation. But some of the extracts such as anise and saffron have not only inhibitory effects but also aggravated this event and have proglycation properties. In accordance with the results obtained we can conclude that wild caraway, turmeric, cardamom and black pepper especially wild caraway extracts are potent antiglycation agents, which can be of great value in the preventive glycation-associated complications in diabetes.

Antioxidant activities of Juniperus foetidissima essential oils against several oxidative systems

The present study aimed to evaluate the antioxidant activity of essential oils obtained from branchlets of male and female trees as well as fruits of Juniperus foetidissima Willd., Cupressaceae, from Iran. For this purpose, essential oils of J. foetidissima were phytochemically analyzed and different concentrations of them were tested in five oxidative systems: 1) low-density lipoprotein oxidation; 2) linoleic acid peroxidation; 3) red blood cell hemolysis; 4) hemoglobin glycation; and 5) insulin glycation assays. In all employed systems, antioxidant effects were observed from the three tested oils though in varying degrees. The most promising activities of the oils were observed against hemoglobin and insulin glycation. Antioxidant activities of the oils did not appear to be dose-dependent. In addition, no consistent superiority in antioxidant effects was observed from a single oil in different assays. In view of the current results, J. foetidissima branchlet and fruit oils could be regarded as effective natural products with anti-glycation activity.

The outcome of induction therapy with monoclonal antibodies in kidney transplantation among Iranian patients: a prospective study.

INTRODUCTION: The administration of interlukin-2 receptor antagonists for induction therapy has reduced the incidence of acute rejection episodes in kidney transplantation. Although some studies have investigated the efficacy of these monoclonal antibodies, there is little experience among Iranian kidney transplant recipients. MATERIALS AND METHODS: Forty-three patients randomly divided into 2 groups were prospectively followed for 3.4 years. Eighteen patients received 2 doses of basiliximab (group I) and another 25 patients received 5 doses of daclizumab (group II). The posttransplantation complications, last serum creatinine level, as well as graft and patient survival rates were compared to investigate the efficacy of these therapies. RESULTS: Among 43 patients, 11.6% experienced acute rejection episodes: 22.2% in group I and 4% in group II (P > .05). In this study, 4.6% of recipients underwent graft nephrectomy: 11.1% in group I and 4% in group II (P > .05). The mortality rate was 4.6%: 5.5% in group I and 4% in group II (P > .05). The mean serum creatinine level was 1.47 +/- 0.7 mg/dL. Although it was lower in group I, the difference was not significant. The 1-year graft and patient survival rates were 90.6% and 95.3%, respectively, with no significant differences between the groups. DISCUSSION: Although induction therapy with monoclonal antibodies may reduce the incidence of acute rejection episodes, graft and patient survival rates were unchanged compared with conventional therapies. Also, there were no significant differences between the results of induction therapy with basiliximab and daclizumab.

Living or deceased donor kidney transplantation: a comparison of results and survival rates among Iranian patients.

OBJECTIVE: Kidney transplantation is the selective treatment of end-stage renal disease. Although most previous studies have concluded that living kidney donation achieves better graft survival, some factors may limit this type of donation. This study investigated the survival rates of living and deceased donor kidney transplantations among Iranian patients. MATERIALS AND METHODS: The records of kidney transplantations up to year 2005 were used to compare 50 deceased (group I) with 50 living donor transplants (group II). The recipients were matched by transplantation time. We used SPSS version 15 software to analyze the data. RESULTS: Group I patients included 28 males and 22 females of mean age of 38 +/- 13 years, while 26 males and 24 females in group II had a mean age of 34.6 +/- 14 years. The rejection and graft nephrectomy rates were significantly higher among group I than group II (P = .01, P = .02). The first-year graft survival was higher in group II (P = .001). The graft survival was significantly lower in recipients who needed a biopsy or dialysis (P = .006 and P = .02, respectively) and higher among those who had a urine volume >4200 mL within the first 24 hours after transplantation (P = .003). Patient survivals were not significantly different between the groups. CONCLUSION: Living donor kidney transplantations showed higher graft survival and lower acute rejection rates compared with those from deceased donors.

Benign and malignant skin lesions in renal transplant recipients.

BACKGROUND: Skin lesions - benign and malignant - occur frequently in organ transplant recipients receiving long-term immunosuppressive therapy. These patients are at greater risk of skin cancers. AIMS: To study dermatologic problems in renal transplant recipients (RTRs). METHODS: One hundred patients (53 men and 47 women) were consecutively examined for benign and malignant skin complications since transplantation in Razi Hospital in Tehran Medical University. The main immunosuppressive therapy regimen in these patients was a combination of prednisolone, azathioprine, and cyclosporine. RESULTS: The early and most common complication was cosmetic side effects that occurred in 98% patients. Skin infections occurred in 83% of the patients and most of them were viral infections (65%), especially of human papilloma viruses (HPVs) in 40% of the patients. We found six cases of malignancy in these patients in that four cases were skin cancers, including one case of SCC, one BCC, and two cases of Kaposi's sarcoma. Dermatologic problems occur most frequently in RTRs, especially skin cancers which have higher frequency in these patients than general population, particularly, Kaposi sarcoma. Sun exposure has an important role in developing epithelial skin cancers following transplantation. The age of developing skin cancer in these patients was early than normal population. CONCLUSION: Our results emphasize the importance of dermatologic examinations and monitoring RTRs to obtain an early diagnosis and treatment of cutaneous manifestations.

Effects of dietary red clover on blood factors and cardiovascular fatty streak formation in hypercholesterolemic rabbits.

Phytoestrogens with a biological activity like estradiol are naturally found in many plants. This study was designed to investigate the effect of red clover, a phytoestrogen-rich member of the legume family (Trifolium pratense) on the development of atherosclerosis in male hyperlipidemic rabbits. Twenty rabbits were semi-randomly distributed into four groups of five each. Two groups received either normal diet or normal diet supplemented with red clover. Two other groups received similar diets to both of which 1% cholesterol was added. Dietary use of red clover (RC) in hyperlipidemic rabbits significantly decreased C-reactive protein (CRP), triglyceride (TG), total cholesterol and LDL-cholesterol (LDL-C) whereas, HDL-cholesterol (HDL-C) was significantly increased in those animals (p < 0.05). Fatty streak formation was also significantly lower in aorta and left and right coronary arteries in the same animals due to use of dietary RC supplementation. These findings suggest that dietary RC may reduce cardiovascular risk factors.

Evaluation of hepatoprotective potential of HESA-A (a marine compound) pretreatment against thioacetamide-induced hepatic damage in rabbits.

HESA-A, a marine compound, has been shown to exhibit antihepatic cancer, antitumor and anti-Parkinson effects. The hepatoprotective potential of HESA-A pretreatment at doses of 125 mg and 250 mg per day orally for a period of 40 days was evaluated against thioacetamide-induced liver damage in rabbits. Biochemical parameters such as serum glutamate oxaloacetate transaminase and lactate dehydrogenase in serum were estimated to assess liver function and lipid peroxidation products (malondialdehyde [MDA]) and the antierythrocyte lysis effect of plasma for measurement of antioxidant potential capacity. Data on the hepatic biochemical parameters revealed the hepatoprotective potential of HESA-A pretreatment against thioacetamide-induced hepatotoxicity in rabbits. There was an increase in total antioxidant and antierythrocyte lysis and a decrease in MDA in plasma after HESA-A treatment. These results strongly suggest that HESA-A has a protective action against preoperative damage to biomembranes.

Mitochondrial DNA and Y-chromosome variation in the caucasus.

We have analyzed mtDNA HVI sequences and Y chromosome haplogroups based on 11 binary markers in 371 individuals, from 11 populations in the Caucasus and the neighbouring countries of Turkey and Iran. Y chromosome haplogroup diversity in the Caucasus was almost as high as in Central Asia and the Near East, and significantly higher than in Europe. More than 27% of the variance in Y-haplogroups can be attributed to differences between populations, whereas mtDNA showed much lower heterogeneity between populations (less then 5%), suggesting a strong influence of patrilocal social structure. Several groups from the highland region of the Caucasus exhibited low diversity and high differentiation for either or both genetic systems, reflecting enhanced genetic drift in these small, isolated populations. Overall, the Caucasus groups showed greater similarity with West Asian than with European groups for both genetic systems, although this similarity was much more pronounced for the Y chromosome than for mtDNA, suggesting that male-mediated migrations from West Asia have influenced the genetic structure of Caucasus populations.

Antihypertensive effect of Iranian Crataegus curvisepala Lind.: a randomized, double-blind study.

The aim of the present study was to investigate the potential antihypertensive effects of extracts of the flavonoid-rich Iranian flower, Crataegus curvisepala Lind., a member of the Rosaceae family. The hydroalcoholic extract of the leaves and flowers were studied in a double-blind, placebo-controlled clinical trial to determine its effects. A total of 92 men and women with primary mild hypertension, aged 40-60 years, were selected and divided randomly into two groups, receiving either hydroalcoholic extract of C. curvisepala Lind. or placebo three times daily for more than 4 months. Blood pressure (BP) was measured each month. Statistical analysis was carried out using Student's t-test. The results obtained showed a significant decrease in both systolic and diastolic BP after 3 months (p < 0.05). C. curvisepala has a time-dependent antihypertensive effect.

In vitro effect of nicotine and cotinine on the susceptibility of LDL oxidation and hemoglobin glycosylation.

Nicotine, a major component of cigarette smoke, plays an important role in the development of cardiovascular disease and lung cancer in smokers. This study was designed to determine the in vitro effects of nicotine and its metabolite cotinine on the susceptibility of LDL to oxidation and hemoglobin glycosylation. Three different concentrations of each one (10, 15, 25 microg/ml) were used. Our data show that nicotine and cotinine are inhibitors for Cu(2+)-induced LDL oxidation but also they increase the glycosylation degree of hemoglobin. Nicotine at final concentrations of (10, 15, 25 microg/ml) increases the rate of hemoglobin glycosylation 25, 32 and 47%, respectively, and cotinine at final concentrations increase the rate of glycosylation 8, 10 and 12%, respectively. Therefore promoting hemoglobin glycosylation is one of the alternations caused by smoking that increase risk of cardiovascular disease.

Garlic induces a shift in cytokine pattern in Leishmania major-infected BALB/c mice.

The regulation of T helper (Th)1- and Th2-type cytokine patterns is important in the final outcome of leishmaniasis in human and murine models. We examined the efficacy of garlic therapy or a combination of garlic and an antimonial drug (glucantime) in promoting healing and regulation of Th1/Th2 cytokine patterns in highly susceptible BALB/c mice infected with Leishmania major. Separate groups of infected mice received 20 mg/kg/day garlic, 60 mg/kg/day glucantime or a combination of the two, from day 30 after infection for 2 weeks. An enzyme-linked immunosorbant assay (ELISA) was performed on spleen cell culture supernatants for interferon(IFN)-gamma interleukin(IL)-2, IL-4 and IL-10. The results indicate that garlic therapy is more effective than the usual antileishmanial drug in curing the infection. Garlic-treated mice developed Th1-type cytokine responses. In contrast, glucantime therapy led to a Th2-type response in the control group with a lower level of IL-2. However, a combination of garlic and glucantime treatment was more effective than either treatment alone, and resulted in a Th1-type response similar to that which developed with garlic treatment. These results suggest that garlic extract in combination with an antimonial drug, may provide effective therapy against L. major. The immunomodulatory properties of garlic were elucidated in terms of shifting the cytokine response to a Th1-type pattern and therefore causing the protective response.

Antihypertensive and antihyperlipidemic effects of Achillea wilhelmsii.

Achillea wilhelmsii C. Koch (Asteraceae) is widely found in different parts of Iran. This plant is full of flavonoids and sesquiterpene lactones, which have been shown to be effective in lowering blood lipids and hypertension. We conducted a double-blind placebo controlled clinical trial to study the antihyperlipidemic and antihypertensive effects of Achillea drops. We randomly selected 120 men and women, aged 40-60 years, and divided them in two distinct groups of moderate hyperlipidemic and primary hypertensive subjects. They were treated either with hydroalcoholic extract or with placebo in the form of 15-20 drops twice daily for more than 6 months. Blood pressure and serum lipids (total cholesterol, triglyceride, low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol) were measured in the groups for 3 periods of 2 months each. The mean and standard deviation of alternations in these variables between the group taking placebo and that taking drugs was calculated by Student's t-test. The results showed a significant decrease in triglycerides after of 2 months while decreases in triglycerides, total cholesterol and LDL-cholesterol were significant after 4 months. Levels of HDL-cholesterol were significantly increased after 6 months' treatment. A significant decrease was observed in diastolic and systolic blood pressure after 2 and 6 months, respectively (p < 0.05).

The effect of fasting in Ramadan on the values and interrelations between biochemical, coagulation and hematological factors.

BACKGROUND: The possible consequences of the long intermittent fasting schedule during Ramadan (one month of food and water intake limited to night hours, a practice that is followed by the majority of the Muslims worldwide) on certain biochemical constituents or coagulation variables have not been extensively documented. PATIENTS AND METHODS: During the month of Ramadan and two months after, we monitored the concentration of different plasma lipoproteins, lipoprotein (a) [Lp(a)], apoproteins A(1) and B, fibrinogen, factor VII activity and some selected hematological factors in 50 healthy subjects who were employees of institutes related to the Isfahan University of Medical Sciences and aged between 30 and 45 years. The effect of fasting in Ramadan on the relationship between biochemical and coagulation variables was also investigated. RESULTS: The values of apoprotein B, Lp(a) and low-density lipoprotein cholesterol (LDL-C)/high-density lipoprotein cholesterol (HDL-C) ratio were significantly decreased during Ramadan (P<0.05), while total cholesterol (Tot-C), triglycerides (TG), LDL-C, HDL-C and fasting blood glucose did not change during that month. Among coagulation and hematological factors, fibrinogen level and factor VII activity were significantly decreased during the month (P<0.05). Results also indicated a significant positive association between fibrinogen level and Lp(a), factor VII activity and Tot-C, LDL-C, TG and Apo B during Ramadan. CONCLUSION: Our findings contribute to a better understanding of previous reports, as the metabolic and coagulation changes that are considered as atherosclerosis risk factors are counterbalanced during Ramadan.

Anti-oxidant effect of flavonoids on hemoglobin glycosylation.

A high glucose concentration has been found to lead to the glycosylation of amino groups of lysine residue in proteins. The addition of reducing agent not only prevents this reaction but also reverses it. On the other hand, flavonoids which found in plant sources have antioxidant properties. Since the glycosylation of protein is an oxidation reaction, therefore, antioxidants should be able to prevent this reaction. In this study, the best concentration and time to incubate glucose with hemoglobin was investigated. Then the glycosylation degree of hemoglobin in the presence of flavonoids and their absence was measured by means of a colorimetric method. Different concentration of flavonoids (Quercetin, Rutin, Kaempferol) were used. The preventing effect on hemoglobin glycosylation by the three concentrations; 0.5, 5, 10 micrograms/ml was estimated as follows: for Rutin; 11%, 27%, 42%, Quercetin; 3%, 37%, 52%, Kaempferol; 10%, 12%, 15% respectively. So, the in vivo effect should be investigated and then plants that containing flavonoids can be utilized to prevent or treat complication of diabetes.