Long-term follow-up of Iranian male patients with systemic lupus erythematosus.

This study was conducted to investigate the long-term survival in male patients with systemic lupus erythematosus (SLE) and its predictors. The main demographic and clinical manifestations at the time of disease diagnosis were recorded retrospectively. Kaplan-Meier curves were used to calculate survival rates. Predictors of mortality were determined by backward Cox regression analysis. Eighty-four male patients with SLE were enrolled. During the 23-year study period, 11 patients died. Lupus nephritis (5 cases), infections (5 cases) and alveolar hemorrhage (1 case) were the most common causes of deaths. Overall survival rates at the end of 5, 10, 15, and 20 years after SLE disease diagnosis were 86%, 84%, 84% and 84%, respectively. In multivariate backward-regression analysis, the main determinants of death at the time of SLE diagnosis were oral ulcer (p = 0.004, HR = 7.69, 95% CI 1.92-33.33), thrombocytopenia (p = 0.012, HR = 5, 95% CI 1.41-16.66) and SLE disease activity index (SLEDAI, p = 0.05, HR = 1.08, 95% CI = 0.999-1.1). Observing oral ulcer, thrombocytopenia and high SLEDAI at the time of disease diagnosis were the main prognostic factors in male lupus patients.

Efficacy of an Oral Solution Containing Five Herbal Extracts in the Treatment of Urolithiasis: A Randomized, Single-blind, Placebo-controlled Clinical Trial.

Objective: The high prevalence of urolithiasis and its recurrence entail the preparation of an efficient drug with the least side effects. Tribulus terrestris, Urtica dioica, Adiantum capillus-veneris, Stigma maydis (corn silk), and Cucumis melo are herbal remedies utilized in traditional medicine for urolithiasis. This study aimed to assess the efficiency of these plants' extracts in treating urolithiasis. Methods: In a randomized, single-blind, placebo-controlled clinical trial, participants meeting inclusion criteria were randomly allocated to the drug (n = 27) and placebo (n = 27) groups to take herbal or placebo solutions, respectively, at a dose of 60 drops 3 times daily for 4 weeks with standard treatment. Before and after the intervention, 24-h urine volume and the quantities of calcium, sodium, citrate, oxalate, urea, creatinine, and uric acid in 24-h urine, and urinary pH were measured. The number and size (diameter in mm) of stones were determined by ultrasonography and recorded for each patient. Findings: Except for 24 h urine volume, other urinary parameters did not alter significantly at the end of the intervention compared to baseline. Furthermore, the two groups had no significant difference regarding these indices. Regarding stone parameters, the stone size decreased significantly in the drug group compared to the placebo group (P = 0.049). The number of cases with complete stone expulsion in the drug group was significantly higher than in the placebo group (12 cases vs. 4 cases, respectively, P = 0.017). Conclusion: Oral consumption of the herbal solution causes stone size reduction and stone expulsion in patients with urolithiasis.

A Study on the Presence of Osteopontin and α3ß1 Integrin in the Endometrium of Diabetic Rats at the Time of Embryo Implantation.

BACKGROUND: Embryo implantation is a critical and multifactorial phenomenon which can be affected by any alteration in molecular micro construction of endometrium. The aim of the current study was to evaluate the effects of diabetes on osteopontin (OPN) and α3ß1 integrin proteins level at the time of endometrial receptivity. METHODS: Twenty-eight female rats were divided into control, diabetic, pioglitazone-treated and metformin-treated groups. Western blot was performed to determine the OPN and α3ß1 integrin proteins in rats' endometrium at the time of implantation. Data were analyzed by analysis of variance (ANOVA) and p<0.05 was considered statistically significant. RESULTS: OPN increased significantly in the diabetic group in comparison with control (p<0.001), metformin-treated (p=0.008) and pioglitazone-treated groups (p< 0.001). Furthermore, α3ß1 integrin protein level in diabetic group had a significant difference in comparison with that of the control (p<0.001), metformin-treated (p= 0.026) and pioglitazone-treated groups (p<0.001). CONCLUSION: OPN and α3ß1 integrin proteins are involved in embryo implantation and their changes in diabetic condition can affect fertility. Treatment with pioglitazone and metformin improved the level of OPN and α3ß1 integrin proteins while pioglitazone was more effective.

Fenofibrate-induced renal dysfunction, yes or no?

In the treatment process of hypertriglyceridemia and diabetic nephropathy in type 2 diabetes, fenofibrate (FEN) is a well-known medication. FEN is from fibrate class drugs that using orally; however, as a side effect, it is associated with serum creatinine level increasing. The aim of this review was to determine the real effect of FEN therapy on renal functions based on both experimental and clinical studies. For this review, using the keywords of "fenofibrate" and "renal" and "function," a variety of sources of information banks, including PubMed, Google Scholar, and Scopus, were used, and the published articles were considered and interpreted. Followed by searching in databases, 45 articles were collected. After screening these articles, based on the study source, they were devided into two parts: 23 articles on animal experiments and 22 articles clinical experiments. Based on this information, it seems that the protective mechanism of FEN is related to vascular endothelial functions. The increased creatinine by FEN is related to different sensitivities to FEN effects caused by a polymorphism in different patients. In patients with normal renal function, follow-up of serum creatinine would be necessary after FEN, but the discontinuation of FEN is not recommended. In addition, in diabetic patients with hypertriglyceridemia, FEN treatment would be suggested for protecting the kidney from diabetes-induced renal injury.

Diabetes mellitus increased integrins gene expression in rat endometrium at the time of embryo implantation.

BACKGROUND: Diabetes mellitus deeply changes the genes expression of integrin (Itg) subunits in several cells and tissues such as monocytes, arterial endothelium, kidney glomerular cells, retina. Furthermore, hyperglycemia could impress and reduce the rate of successful assisted as well as non-assisted pregnancy. Endometrium undergoes thorough changes in normal menstrual cycle and the question is: What happens in the endometrium under diabetic condition? OBJECTIVE: The aim of the current study was to investigate the endometrial gene expression of α3, α4, αv, Itg ß1 and ß3 subunits in diabetic rat models at the time of embryo implantation. MATERIALS AND METHODS: Twenty-eight rats were randomly divided into 4 groups: control group, diabetic group, pioglitazone-treated group, and metformin-treated group. Real-time PCR was performed to determine changes in the expression of Itg α3, α4, αv, ß1, and ß3 genes in rat's endometrium. RESULTS: The expression of all Itg subunits increased significantly in diabetic rats' endometrium compared with control group. Treatment with pioglitazone significantly reduced the level of Itg subunits gene expression compared with diabetic rats. While metformin had a different effect on α3 and α4 and elevated these two subunits gene expression. CONCLUSION: Diabetes mellitus significantly increased the expression of studied Itg subunits, therefore untreated diabetes could be potentially assumed as one of the preliminary elements in embryo implantation failure.

Impact of Metformin and Pioglitazone on Serum Level of Tumor Necrosis Factor-Alpha and Lipid Profiles during Implantation Window in Diabetic Rats.

BACKGROUND: The present study was designed to evaluate serum lipid profile and tumor necrosis factor-alpha (TNF-ɑ) level in diabetic rats at implantation time. Type 2 diabetes mellitus (T2DM) could affect various systems, including innate immune system and it causes chronic low-grade inflammation, increasing level of TNF-ɑ. Furthermore, T2DM is often accompanied by impaired lipid profile. Metformin and pioglitazone are used as the first and second lines of treatment for T2DM. MATERIALS AND METHODS: In this experimental study, 35 adult virgin female wistar rats, weighting 175-225 g, were randomly categorized into five groups: i. Control, ii. Sham, iii. Nicotinamide (NA)+streptozotocin (STZ) induced T2DM, iv. Diabetic+pioglitazone (20 mg/kg/day for 28 days oral administration), and v. Diabetic+metformin (100 mg/kg/day for 28 days oral administration). At the time of implantation, TNF-ɑ level in serum of rats was measured by ELISA kit. Glucose was measured using photometric method and lipid profiles were calculated by enzymatic methods. RESULTS: Level of TNF-ɑ in the diabetic group was significantly higher than other groups (P<0.001). In metformin treated group, TNF-ɑ serum level was also significantly higher than pioglitazone treated group (P<0.001). Fasting blood sugar (FBS) and lipid profiles were significantly higher in diabetic group. CONCLUSION: Metformin and pioglitazone have similar effects on glucose, lipid profiles and TNF-ɑ serum levels. Among these drugs, pioglitazone has more efficient influence on TNF-α serum level, in comparison with metformin.

Evaluation of Osteopontin Gene Expression in Endometrium of Diabetic Rat Models Treated with Metformin and Pioglitazone.

BACKGROUND: Osteopontin (Opn) is one of the co-factors involved in cell adhesion and invasion during the implantation process. Several reports have shown Opn expression changes in diabetic condition in several tissues. In addition, an increased incidence of spontaneous abortion is reported in diabetic women. We, therefore, designed a study to evaluate the effects of diabetes on Opn expression at implantation time after treatment with metformin and pioglitazone. MATERIALS AND METHODS: In this interventional and experimental study, 28 rats were randomly divided into four groups, namely control, diabetic, pioglitazone-treated diabetic rats and metformin-treated diabetic rats. Streptozotocin (STZ) and nicotinamide (NA) were used to induce type 2 diabetes (T2D). During the implantation window, the endometrium was removed and the expression of Opn was analysed by reverse transcription quantitative polymerase chain reaction (RT-qPCR). RESULTS: Opn expression was significantly higher (30.70 fold-changes) in the diabetic group in comparison with the control group (P=0.04). Furthermore, the expression of Opn was significantly lower in the diabetic group treated with pioglitazone when compared with the diabetic group (P=0.04). CONCLUSION: According to the high Opn expression and the possibility of increased adhesion of endometrial epithelial cells, the invasion of blastocyst may be affected and thus reduced. As pioglitazone significantly reversed the upregulation of Opn in diabetic rats, it may be considered as a therapeutic compound for treating T2D.

Incidence of nonmelanoma skin cancer in renal transplant recipients: A systematic review and meta-analysis.

BACKGROUND: Nonmelanoma skin cancer (NMSC) in renal transplant recipients is common and associated with significant morbidity and mortality. The aim of the present systematic review and meta-analysis was to estimate the incidence of NMSC among renal transplant recipients. MATERIALS AND METHODS: We systematically searched PubMed, Medline, Scopus, and Web of Science databases for studies that assessed the incidence of NMSC in renal transplant recipients using a combination of relevant keywords. Two independent investigators included studies and extracted necessary information. Random effect meta-analysis was used to estimate pooled incidence of NMSC with 95% confidence intervals (CIs). RESULTS: Twenty-nine studies comprising 36,021 patients meet the criteria for the systematic review. The pooled incidence of NMSC in renal transplant recipients was 12.6% (95% CI: 12%-14%) with a majority of squamous cell carcinoma (SCC) 55% (95% CI: 47%-63%). The pooled estimate of the incidence rates of SCC and basal cell carcinoma was 2.7% (95% CI: 2%-3.4%) and 2.2% (95% CI: 1.5%-2.8%), respectively. Subgroup analysis per geographic location showed that pooled incidence of NMSC was 39.1% (95% CI: 26.3%-51.8%), 12.4% (95% CI: 8.8%-16%), and 1.2% (95% CI: 0.4%-2%) in Australia and New Zealand, Europe, and Middle East, respectively. CONCLUSION: The results of the current meta-analysis demonstrated that the incidence of NMSC in renal transplant recipients varies widely. Regarding the high incidence of NMSC among renal transplant recipients, awareness of associated risk factors and early diagnosis of the malignancy in the population is a major clinical need.

Childhood versus adult-onset systemic lupus erythematosus: long-term outcome and predictors of mortality.

The aim of this study was to compare survival of childhood-onset systemic lupus erythematosus (c-SLE) and adult-onset SLE (a-SLE) according to initial manifestations. This was a retrospective cohort study. All patients were categorized into c-SLE (≤18 years) and a-SLE (>18 years). The clinical and serological data at the time of diagnosis were recorded and compared. Kaplan-Meier curves were used to compare survival rates between the two groups. Predictors of mortality were obtained by a backward Cox regression. One hundred eighty patients with c-SLE and 394 patients with a-SLE were enrolled. The female/male ratio was higher in c-SLE (P = 0.0001). Lupus nephritis (P = 0.002) and valvular heart disease (P = 0.025) were more common in c-SLE and a-SLE, respectively. In a 23-year follow-up, 20 patients (11.1%) with c-SLE and 35 patients (8.9%) with a-SLE died. Mortality was not significantly different between them (P = 0.4). The main causes of death were nephritis (50% in c-SLE vs. 29% in a-SLE), infections (40% in c-SLE vs. 29% in a-SLE), and circulatory disease (10% in c-SLE vs. 37% in a-SLE). The difference was not significant (P = 0.08). Cumulative survival rates after 5, 10, 15, and 20 years were 91, 87, 85, and 78% in c-SLE and 93, 90, 90, and 83% in a-SLE, respectively. By multivariate analysis, seizure, proteinuria, and nephritis in c-SLE and seizure, hematuria, and pericarditis in a-SLE had negative prognostic effect on survival. Both c-SLE and a-SLE patients with seizure or renal involvement should be monitored more carefully to prevent ominous outcomes.

The association between initial manifestations of childhood-onset systemic lupus erythematosus and the survival.

INTRODUCTION: Childhood-onset systemic lupus erythematosus (cSLE) comprises 15-20% of patients with SLE. Although several studies have reported the outcomes of adult-onset SLE, few investigations have been conducted on cSLE in the Middle East. METHODS: In a retrospective study, all children with SLE admitted to our tertiary referral center between 1992 and 2011 were recruited. The clinical and laboratory data at the time of onset were recorded and analyzed. Kaplan-Meier analysis was used to calculate the survival rates. Cox regression analysis was applied to assess the predictors of mortality. RESULTS: One hundred and eighty-eight children diagnosed with SLE were enrolled during the study period. Nine patients were censored due to loss to follow-up (6) and incomplete data (3 cases). Mean age of patients at the time of onset was 14.4 (3.05) years. Only 22 (11.8%) children were younger than 10 years at the time of disease onset. In total, 20 patients (11%) died, all after the first decade of life. The most common cause of death was lupus nephritis (10 patients, 50% of deaths) followed by infections (35%), cerebrovascular accidents (10%) and alveolar hemorrhage (5%). Cumulative survival rate after 5, 10, 15 and 20 years was 91, 87, 85, and 79%, respectively. Having hematuria or pleurisy at the time of SLE onset had a negative effect on survival in multivariate analysis. CONCLUSION: cSLE survival in Iran was comparable to that in other developing countries. Baseline presentation with hematuria predominantly increased the mortality rate in cSLE. Prospective and larger studies in future may unfold other aspects of cSLE.

Robotic Delivery of Complex Radiation Volumes for Small Animal Research.

The Small Animal Radiation Research Platform (SARRP) is a novel and complete system capable of delivering multidirectional (focal), kilo-voltage radiation fields to targets in small animals under robotic control using cone-beam CT (CBCT) image guidance. The capability of the SARRP to deliver highly focused beams to multiple animal models provides new research opportunities that more realistically bridge laboratory research and clinical translation. This paper describes the design and operation of the SARRP for precise radiation delivery. Different delivery procedures are presented which enable the system to radiate through a series of points, representative of a complex shape. A particularly interesting case is shell dose irradiation, where the goal is to deliver a high dose of radiation to the shape surface, with minimal dose to the shape interior. The ability to deliver a dose shell allows mechanistic research of how a tumor interacts with its microenvironment to sustain its growth and lead to its resistance or recurrence.

Image-guided small animal radiation research platform: calibration of treatment beam alignment.

Small animal research allows detailed study of biological processes, disease progression and response to therapy with the potential to provide a natural bridge to the clinical environment. The small animal radiation research platform (SARRP) is a portable system for precision irradiation with beam sizes down to approximately 0.5 mm and optimally planned radiation with on-board cone-beam CT (CBCT) guidance. This paper focuses on the geometric calibration of the system for high-precision irradiation. A novel technique for the calibration of the treatment beam is presented, which employs an x-ray camera whose precise positioning need not be known. Using the camera system we acquired a digitally reconstructed 3D 'star shot' for gantry calibration and then developed a technique to align each beam to a common isocenter with the robotic animal positioning stages. The calibration incorporates localization by cone-beam CT guidance. Uncorrected offsets of the beams with respect to the calibration origin ranged from 0.4 mm to 5.2 mm. With corrections, these alignment errors can be reduced to the sub-millimeter range. The calibration technique was used to deliver a stereotactic-like arc treatment to a phantom constructed with EBT Gafchromic films. All beams were shown to intersect at a common isocenter with a measured beam (FWHM) of approximately 1.07 mm using the 0.5 mm collimated beam. The desired positioning accuracy of the SARRP is 0.25 mm and the results indicate an accuracy of 0.2 mm. To fully realize the radiation localization capabilities of the SARRP, precise geometric calibration is required, as with any such system. The x-ray camera-based technique presented here provides a straightforward and semi-automatic method for system calibration.

Precision radiotherapy for small animal research.

Preclinical research using well characterized small animal models has provided tremendous benefits to medical research, enabling low cost, large scale trials with high statistical significance of observed effects. The goal of the Small Animal Radiation Research Platform (SARRP) is to make those models available for the development and evaluation of novel radiation therapies. SARRP demonstrates the capabilities of delivering high resolution, sub-millimeter, optimally planned conformal of radiation with on-board cone-beam CT (CBCT) guidance. The system requires accurate calibration of the x-ray beam for both imaging and radiation treatment. In this paper, we present a novel technique using an x-ray camera for calibration of the treatment beam. This technique does not require precise positioning or calibration of the x-ray camera.

High-resolution, small animal radiation research platform with x-ray tomographic guidance capabilities.

PURPOSE: To demonstrate the computed tomography, conformal irradiation, and treatment planning capabilities of a small animal radiation research platform (SARRP). METHODS AND MATERIALS: The SARRP uses a dual-focal spot, constant voltage X-ray source mounted on a gantry with a source-to-isocenter distance of 35 cm. Gantry rotation is limited to 120 degrees from vertical. X-rays of 80-100 kVp from the smaller 0.4-mm focal spot are used for imaging. Both 0.4-mm and 3.0-mm focal spots operate at 225 kVp for irradiation. Robotic translate/rotate stages are used to position the animal. Cone-beam computed tomography is achieved by rotating the horizontal animal between the stationary X-ray source and a flat-panel detector. The radiation beams range from 0.5 mm in diameter to 60 x 60 mm(2). Dosimetry is measured with radiochromic films. Monte Carlo dose calculations are used for treatment planning. The combination of gantry and robotic stage motions facilitate conformal irradiation. RESULTS: The SARRP spans 3 ft x 4 ft x 6 ft (width x length x height). Depending on the filtration, the isocenter dose outputs at a 1-cm depth in water were 22-375 cGy/min from the smallest to the largest radiation fields. The 20-80% dose falloff spanned 0.16 mm. Cone-beam computed tomography with 0.6 x 0.6 x 0.6 mm(3) voxel resolution was acquired with a dose of <1 cGy. Treatment planning was performed at submillimeter resolution. CONCLUSION: The capability of the SARRP to deliver highly focal beams to multiple animal model systems provides new research opportunities that more realistically bridge laboratory research and clinical translation.

Small animal radiation research platform: imaging, mechanics, control and calibration.

In cancer research, well characterized small animal models of human cancer, such as transgenic mice, have greatly accelerated the pace of development of cancer treatments. The goal of the Small Animal Radiation Research Platform (SARRP) is to make those same models available for the development and evaluation of novel radiation therapies. In combination with advanced imaging methods, small animal research allows detailed study of biological processes, disease progression, and response to therapy, with the potential to provide a natural bridge to the clinical environment. The SARRP will realistically model human radiation treatment methods in standard animal models. In this paper, we describe the mechanical and control structure of the system. This system requires accurate calibration of the x-ray beam for both imaging and radiation treatment, which is presented in detail in the paper.