Renal vein thrombosis due to metastatic germ cell tumor, report of a case with a very rare clinical scenario.

BACKGROUND: Renal metastasis is a rare manifestation of germ cell tumors. Extension of malignant lesions into the renal vein can complicate the scenario. CASE: This report presents a 35-year-old man with primary stage IS NSGCT. Fourteen months after radical orchiectomy he presented with metastasis in the lung, kidney, and para-aortic lymph nodes. He received multiple lines of salvage treatments including chemotherapy and surgery. Intraoperative exploration during radical nephrectomy and retroperitoneal lymphadenectomy revealed intra-renal vein involvement with a prominent teratomatous component. CONCLUSION: Defining the exact extent of malignant lesions, especially endovascular lesions, is very important to clarify how advanced the malignant lesions are. The surgeons must be aware of the risk factors that predict vascular involvement, and therefore, providing intraoperative access to vascular surgery procedures when needed.

The In Vitro Pro-inflammatory Functions of the SP/NK1R System in Prostate Cancer: a Focus on Nuclear Factor-Kappa B (NF-κB) and Its Pro-inflammatory Target Genes.

Prostate cancer is one of the main global health threats for men which is in close association with chronic inflammation. Neuropeptide substance P (SP), acting through neurokinin receptor (NK-1R), induces various pro-inflammatory responses which are strongly involved in the pathogenesis of several diseases as well as cancer. Therefore, we aimed to investigate the pro-inflammatory functions of the SP/NK1R complex in prostate cancer and the therapeutic effects of its inhibition by NK-1R antagonist, aprepitant, in vitro. MTT assay was conducted for the cytotoxicity assessment of aprepitant in prostate cancer cells. The protein expression levels were evaluated by Western blot assay. Quantitative real-time PCR (qRT-PCR) was applied to measure mRNA expression levels of pro-inflammatory cytokines. Concurrently, the protein concentrations of pro-inflammatory cytokines were also analyzed by enzyme-linked immunosorbent assay. We observed that SP increased the levels of pro-inflammatory cytokines (IL-1ß, IL-6, and TNF-α), while treatment with aprepitant reduced the effects of SP. We also indicated that SP increased the protein levels of nuclear factor-kappa B (NF-κB), as the main regulator of inflammatory processes, and also an NF-κB target gene, cyclooxygenase 2 (COX-2) in prostate cancer cells, while treatment with aprepitant reversed these effects. Taken together, our findings highlight the importance of the SP/NK1R system in the modulation of pro-inflammatory responses in prostate cancer cells and suggest that aprepitant may be developed as a novel anti-inflammatory agent for the management of cancer-associated inflammation.

Pomegranate seed oil protects against tacrolimus-induced toxicity in the heart and kidney by modulation of oxidative stress in rats.

Objective: The clinical use of tacrolimus is limited due to its side effects. This research investigated the protective activities of pomegranate seed oil (PSO) against TAC toxicity. Materials and Methods: The groups are included normal (1 ml of corn oil), TAC (2 mg/kg), and co-treatment of PSO (0.4 and 0.8 ml/kg) and TAC. All administrations were carried out intraperitoneally for 14 days. After the last injection, blood was collected from the heart. Results: TAC increased creatinine and urea. Increased malondialdehyde, reduced thiol content and superoxide dismutase. The elevation of lactate dehydrogenase, aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine kinase-MB and creatinine phosphokinase that confirmed cardiac toxicity. PSO reduced TAC toxicity. PSO decreased TAC-induced pathology injury. Conclusion: PSO reduced TAC toxicity in renal and heart via scavenging free radicals.

Development of targeted gene delivery system based on liposome and PAMAM dendrimer functionalized with hyaluronic acid and TAT peptide: In vitro and in vivo studies.

The development of gene delivery systems is essential to improve their transfection efficiency and cytotoxicity. Combination of lipid and polymeric nanoparticles with the characteristics of both systems have been considered as a next-generation gene delivery platform. In the current study, we designed a novel and efficient targeted gene delivery system based on liposome and PAMAM dendrimer in cancer cells. Two polymeric formulations containing polyamidoamine-TAT (PAMAM-TAT) and PAMAM-TAT-Hyaluronic acid (HA) and two lipopolymeric carriers including PAMAM-TAT-Liposome and PAMAM-TAT-HA-Liposome were complexed with the enhanced green fluorescent protein (EGFP) plasmid and then evaluated in terms of physicochemical characteristics. The cytotoxicity and transfection efficiency of these synthetized carriers were accomplished against murine colon carcinoma cell line (C26). The biodistribution of polyplexes and lipoployplexes was also evaluated in the C26 tumor bearing mice. The results showed no significant toxicity for all designed nanoparticles (NPs) in C/P4. The highest gene expression was observed using lipopolyplex PAMAM-TAT-HA-Liposome in C/P4 (ratio polymer/DNA; wt/wt). Biodistribution study demonstrated more aggregation of targeted lipopolyplex in tumor cells than other nanoparticles (NPs). It could be concluded that the developed targeted lipopolymeric complex could serve as promising nanotherapeutic system for gene therapy.

Adult Wilms with Biphasic Pattern; A Case Report.

BACKGROUND: Wilms' tumor, nephroblastoma, is an extremely uncommon kidney tumor of adulthood. We reported a woman with a huge kidney mass diagnosed with nephroblastoma. CASE PRESENTATION: A 39-year-old female was assessed due to right flank pain. CT scan revealed a mass measuring 128×100 mms involving the upper portion of the right kidney. The patient underwent nephrectomy, and the diagnosis of adult Wilms' tumor was confirmed based on the morphological and immunohistochemical findings. CONCLUSION: In adult patients with flank pain and renal mass, the diagnosis of Wilms' tumor should be pronounced in the absence of histopathologic features of renal cell carcinoma.

Vaso-nervorumitis: responsible for pain in Buerger's disease?

Buerger's disease (BD) is an episodic, inflammatory, and occlusive peripheral vascular disease with unknown etiology, which can lead to tissue or limb loss. BD patients usually present neurological symptoms from the early stages of the disease including numbness, cold sensation, and allodynia as the disease progresses. Pain in the late stages of BD is very severe, almost resistant to opioid pain killers, and sometimes compels the patient to pursue major amputation. Therefore, pain management in BD patients is one of the most important and, at the same time, challenging issues since its main etiology is not well understood. Recently, a 39-year-old male smoker with a diagnosis of BD underwent a below-knee amputation in his left leg. Oddly, we found that the vasa-nervorum of the sural nerve had the pathological changes usually observed in BD, including inflammation and proliferation of endothelial cells. Notably, the inflammation was limited to the vasa-nervorum and did not extend to the nerve fascicles. Our findings could provide a clue to taking the approach of managing pain in BD as if it were vasculitis neuropathy; and the inflammation of the vasa-nervorum individually might be responsible for the pain characteristic of BD. In addition, our findings could indicate that BD is a systemic vasculitis of microcirculation and, hence, a different treatment approach for BD might be needed in addition to antithrombotic and vasodilator.

Protective effect of Rheum turkestanicum root against mercuric chloride-induced hepatorenal toxicity in rats.

OBJECTIVE: The present study was designed to investigate the protective effects of hydroalcoholic extract of Rheum turkestanicum against HgCl2 hepatorenal toxicity in rats. MATERIALS AND METHODS: Animals were randomly divided into five groups (n= 6 in each group) and received HgCl2 and plant's extract, intraperitoneally. Group1 received saline (1 mL/kg/day), group 2 received extract (200 mg/kg/day), group 3 was treated with HgCl2 (5 mg/kg/day,) and groups 4 and 5 received the extract (100 and 200 mg/kg/day, respectively), 1 hr before HgCl2 administration. All injections last for 3 days. Blood samples and specimens of the liver and kidney were collected 24 hr after the last injection. RESULTS: Data showed that HgCl2 significantly increases liver malondialdehyde (MDA) level, reduces total sulfhydryl content and increases serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity, compared to control group. The histopathological changes such as inflammatory cells infiltration was observed in HgCl2-treated group while plant's extract partially improved histological changes. The extract (100 and 200 mg/kg/day) improved the liver functions as reflected by significant reductions in AST and ALT levels in serum, MDA decreased and the content of total sulfhydryl elevated. Also, the extract improved necrosis and atrophy of the kidney induced byHgCl2. Pretreatment with the extract reduced creatinine and urea in serum, and glucose and protein concentrations in urine, compared to HgCl2- treated group (group III). The extract significantly reversed HgCl2-induced depletion in thiol content and elevation in MDA content. CONCLUSION: Therefore, oxidative stress may play an important role in HgCl2-induced hepatorenal injury and R. turkestanicum extract may be regarded as a useful to protect the kidney and liver against HgCl2-induced oxidative damage.

Unexpected Inflammation in the Sympathetic Ganglia in Thromboangiitis Obliterans.

The aim of this study was to inspect more closely the microscopic and molecular sympathetic ganglia histology in thromboangiitis obliterans (TAO). The paraffin block and frozen RNAlater-treated tissue of the lumbar sympathetic ganglia of 19 TAO Caucasian male patients were evaluated. The gene expression of cluster of differentiation 4 (CD4) and cluster of differentiation 8 (CD8) markers in the frozen RNAlater-treated sympathetic ganglia tissues were evaluated by real-time polymerase chain reaction. Unexpectedly, lymphocyte infiltration was observed in all of the histological sections, ranging from scattered to moderate lymphocyte infiltration. In seven patients, five of them underwent below-knee amputation, neutrophil infiltration was observed in addition to lymphocyte infiltration. The gene expression of the CD8 marker in all of the samples with the expression of CD4 markers in only four tissue samples was demonstrated. The expression of CD8 in comparison to CD4 was approximately 4.37-fold changes using Pfaffle method. It appears that inflammation of the sympathetic ganglia plays a role in the pathophysiology of TAO and its outcome. Sympathetic ganglia inflammation may be responsible for general vasoconstriction, vascular inflammation, and the increased risk of thrombotic events, by activating the platelets. The dominant infiltration of T cytotoxic lymphocytes and neutrophils in sympathetic ganglia may probably support the idea of possible intracellular infectious pathogen trigger for TAO and consequently infiltration of pathogen-specific T cells into the sympathetic ganglia in TAO.

Childhood Facial Osteo Sarcoma: a Case Report.

Osteosarcoma (OS) is the eighth common cancer of childhood and its incidence is 4 cases in one million in children younger than 14. Facial OS incidence is estimated between 8 and 10% of OS cases. The main etiology of OS is unknown, but various predisposing factors are proposed such as radiation, radiotherapy, some benign bone diseases like Paget's disease or fibrous dysplasia. There is a 5-year survival rate of 68% and it decreases with the increase of age. Positive history of radiotherapy is the main predisposing factor for childhood OS. There is some evidence about the X-ray induced mutation in genomic DNA that leads to osteosarcoma. In the present paper we present a 19-month old girl with a mass located in the inferior margin of the left cheek and orbit. Our case is unique with regard to her young age and sex. Moreover, the tumor was located in an uncommon site and her disease was progressive and resistant.

The Prognostic Role of Tumor Marker CA-125 in B-Cell non-Hodgkin's Lymphoma.

BACKGROUND: B-cell non-Hodgkin's lymphoma (NHL) is a common malignancy of lymphoid tissues. Different types of NHL show various behaviors, prognoses, and responses to treatment. Evaluation of disease activity in NHL can be helpful in managing and even increasing the patient's survey. METHODS AND RESULTS: In total, 121 patients (76 males and 45 females), and their age range were 18-53 years, were evaluated in this study. The mean level of serum carbohydrate antigen 125 (CA-125) was 89.3±18.5 u/ml, ranging from 27 to 135 u/ml. There were significant differences in International Prognostic Index (IPI) score (p=0.002), stage of the disease (p=0.006), mortality rate (p=0.02), and relapse rate (p=0.04) between patients with serum CA-125 level <35 u/ml and patients with CA-125 level >35 u/ml. CONCLUSION: CA-125 seems to be a useful and reliable tumor marker for monitoring a patient with NHL. It might be the time to consider CA-125 in staging, prognostic scoring, or decision making about NHL treatment.

Is (99m)Tc-MIBI scintigraphy a predictor of response to pre-operative neoadjuvant chemotherapy in Osteosarcoma?

OBJECTIVES: Multidrug resistance (MDR), which may be due to the over expression of P-glycoprotein (Pgp) and/or MRP, is a major problem in neoadjuvant chemotherapy of osteosarcoma. The aim of this study was to investigate the role of Tc-99m MIBI scan for predicting the response to pre-operative chemotherapy. METHODS: Twenty-five patients (12 males and 13 females, aged between 8 and 52y) with osteosarcoma were studied. Before the chemotherapy, planar (99m)Tc-MIBI anterior and posterior images were obtained 10-min [tumor-to-background ratio: (T1/B1)10min] and 3-hr after tracer injection. After completion of chemotherapy, again (99m)Tc-MIBI scan was performed at 10-min after tracer injection. In addition to calculation of decay corrected tumor to background (T/B) ratios, using the 10-min and 3-hr images of the pre-chemotherapy scintigraphy, percent wash-out rate (WR%) of (99m)Tc-MIBI was calculated. Using the 10-min images of the pre- and post-chemotherapy scans, the percent reduction in uptake at the tumor site after treatment (Red%) was also calculated. Then after surgical resection, tumor response was assessed by percentage of necrosis. RESULTS: All patients showed significant (99m)Tc-MIBI uptake in early images. Only 9 patients showed good response to chemotherapy (necrosis≥90%) while 16 patients were considered as non-responder (necrosis<90%). There was no statistical significant difference between non-responders and responders in (T1/B1)10min.There was a significant negative correlation between WR% and percentage of necrosis (P=0.001). On the other hand, there was a significant correlation between Red% and percentage of necrosis (P<0.001).There was also statistical significant difference in WR% and Red% between non-responders and responders (both P< 0.001). CONCLUSION: Washout rate of (99m)Tc-MIBI in pre-chemotherapy scintigraphy as well as Red% using pre- and post-chemotherapy MIBI scintigraphy are useful methods for predicting response to neoadjuvant chemotherapy.

Does a species of Rickettsia play a role in the pathophysiology of Buerger's disease?

Rickettsia is an intracellular pathogen that attaches to vascular endothelial cell membranes and its genome integrates into the DNA of the host and thereby inhibits apoptosis of the endothelial cells. Rickettsia can infect the body following a flea/louse bite. Rickettsia was suggested as one etiology of Buerger's disease long ago. We report a patient with Buerger's disease for whom a left below-knee amputation was done. Twenty-five biopsies for DNA extraction were obtained from the arteries, veins and microvasculature of the amputated limb. Three samples were positive for Rickettsia. The finding may explain the proliferation of endothelial cells in the pathology of Buerger's disease, segmental nature of the disease, involving small- and medium-sized vessels, and the prevalence of Buerger's disease among the low socioeconomic class of the society. Understanding the infectious etiology of Buerger's disease would be invaluable, since early antibiotic therapy or even vaccination might have prevented the limb loss in the current and other cases of Buerger's disease. The authors suggest that paraffin blocks of Buerger's disease biopsies be investigated for Rickettsia infection, focusing specifically on the area of endothelial cell proliferation for DNA extraction. These results should be compared with other biopsies from a variety of other peripheral vascular diseases.

Effects of erythropoietin on electrocardiogram changes in carbon monoxide poisoning: an experimental study in rats.

The aim of this study was to define the electrocardiogram (ECG) changes following the moderate to severe CO intoxication in rats, and also evaluating the effect of erythropoietin (EPO) on observed cardiac disturbances. The growing literature on erythropoietin effect on cardiac ischemia led us to question its effect on cardiotoxicity due to the carbon monoxide poisoning. Wistar rats were exposed to three different concentrations of CO (250 PPM, 1000 PPM or 3000 PPM). EPO was administrated (5000 IU/Kg, intraperitoneal injection) at the end of CO exposure and then the animals were re-oxygenated with ambient air. Subsequently ECG recording, heart rate and carboxyhemoglobin values were evaluated. ECG changes following the CO intoxication included ST segment elevation and depression, T wave inversion and first-degree AV block. Ischemic ECG changes reduced significantly in EPO-treated animals. In the present study, for the first time, EPO was investigated for the management of cardiac complications due to the CO poisoning. Our results showed that EPO could inhibit ischemic changes of ECG after the CO poisoning.

Elevated plasma total homocysteine in preeclampsia.

OBJECTIVES: To investigate the possible association between hyperhomocysteinemia and preeclampsia. METHODS: A case-control study was carried out in the Departments of Obstetrics and Gynecology of the Ghaem Hospitals in Mashhad University of Medical Sciences, Mashhad, Iran from May 2004 to August 2006 and included 75 preeclamptic patients, 37 women with mild preeclampsia, and 38 women with severe preeclampsia, in addition we included 40 controls without pregnancy complications. Plasma total homocysteine was determined in all subjects by enzyme linked immunosorbent assay. RESULTS: The 3 groups were similar in age and body. Patients with severe preeclampsia had significantly higher mean plasma levels (13.8+/-7 mg/l) than normal pregnant women (8.8+/-2.8 mg/l) and mild pre-eclamptic women (10.4+/-2.3 mg/l) (p<0.05). CONCLUSION: Women who developed severe preeclampsia have higher plasma homocysteine levels than women who remain normotensive throughout pregnancy.