Neuroinvasion of SARS-CoV-2 in human and mouse brain.

Although COVID-19 is considered to be primarily a respiratory disease, SARS-CoV-2 affects multiple organ systems including the central nervous system (CNS). Yet, there is no consensus on the consequences of CNS infections. Here, we used three independent approaches to probe the capacity of SARS-CoV-2 to infect the brain. First, using human brain organoids, we observed clear evidence of infection with accompanying metabolic changes in infected and neighboring neurons. However, no evidence for type I interferon responses was detected. We demonstrate that neuronal infection can be prevented by blocking ACE2 with antibodies or by administering cerebrospinal fluid from a COVID-19 patient. Second, using mice overexpressing human ACE2, we demonstrate SARS-CoV-2 neuroinvasion in vivo. Finally, in autopsies from patients who died of COVID-19, we detect SARS-CoV-2 in cortical neurons and note pathological features associated with infection with minimal immune cell infiltrates. These results provide evidence for the neuroinvasive capacity of SARS-CoV-2 and an unexpected consequence of direct infection of neurons by SARS-CoV-2.

Evaluating survival in subjects with astrocytic brain tumors by dynamic susceptibility-weighted perfusion MR imaging.

PURPOSE: Studies have evaluated the application of perfusion MR for predicting survival in patients with astrocytic brain tumors, but few of them statistically adjust their results to reflect the impact of the variability of treatment administered in the patients. Our aim was to analyze the association between the perfusion values and overall survival time, with adjustment for various clinical factors, including initial treatments and follow-up treatments. MATERIALS AND METHODS: This study consisted of 51 patients with astrocytic brain tumors who underwent perfusion-weighted MRI with MultiHance® at a dose of 0.1 mmol/kg prior to initial surgery. We measured the mean rCBV, the 5% & 10% maximum rCBV, and the variation of rCBV in the tumors. Comparisons were made between patients with and without 2-year survival using two-sample t-test or Wilcoxon rank-sum test for the continuous data, or chi-square and Fisher exact tests for categorical data. The multivariate cox-proportional hazard regression was fit to evaluate the association between rCBV and overall survival time, with adjustment for clinical factors. RESULTS: Patients who survived less than 2 years after diagnosis had a higher mean and maximum rCBV and a larger variation of rCBV. After adjusting for clinical factors including therapeutic measures, we found no significant association of overall survival time within 2 years with any of these rCBV values. CONCLUSIONS: Although patients who survived less than 2 years had a higher mean and maximum rCBV and a larger variation of rCBV, rCBV itself may not be used independently for predicting 2-year survival of patients with astrocytic brain tumors.

A solitary extraventricular subependymal giant cell astrocytoma in the absence of tuberous sclerosis.

Subependymal giant cell astrocytomas (SEGAs) are the most common intracranial tumors in Tuberous Sclerosis Complex (TSC). Very few cases of solitary SEGA without a diagnosis of TSC have been described. Most of these previously reported solitary SEGAs were located near the caudothalamic groove or in close proximity to the lateral ventricles. Here, we describe a unique case of solitary extraventricular SEGA in a 17-year-old boy who presented with new-onset seizures in the absence of the clinical and genetic diagnosis of TSC. This extraventricular SEGA was involving white matter and cortex of the occipital lobe and was predominantly hypointense on T1 and T2-weighted images with a markedly hypointense signal on susceptibility-weighted images likely secondary to dense internal calcifications. Solitary SEGA can occur in the extraventricular location in patients without TSC and should be included in the differential diagnosis of a densely calcified supratentorial intra-axial tumor in children, especially during the second decade of life.

Neuroinvasion of SARS-CoV-2 in human and mouse brain.

Although COVID-19 is considered to be primarily a respiratory disease, SARS-CoV-2 affects multiple organ systems including the central nervous system (CNS). Yet, there is no consensus whether the virus can infect the brain, or what the consequences of CNS infection are. Here, we used three independent approaches to probe the capacity of SARS-CoV-2 to infect the brain. First, using human brain organoids, we observed clear evidence of infection with accompanying metabolic changes in the infected and neighboring neurons. However, no evidence for the type I interferon responses was detected. We demonstrate that neuronal infection can be prevented either by blocking ACE2 with antibodies or by administering cerebrospinal fluid from a COVID-19 patient. Second, using mice overexpressing human ACE2, we demonstrate in vivo that SARS-CoV-2 neuroinvasion, but not respiratory infection, is associated with mortality. Finally, in brain autopsy from patients who died of COVID-19, we detect SARS-CoV-2 in the cortical neurons, and note pathologic features associated with infection with minimal immune cell infiltrates. These results provide evidence for the neuroinvasive capacity of SARS-CoV2, and an unexpected consequence of direct infection of neurons by SARS-CoV-2.

Post-operative perfusion and diffusion MR imaging and tumor progression in high-grade gliomas.

PURPOSE: Perfusion and diffusion magnetic resonance imaging (MRI) provide important biomarkers for brain tumor analysis. Our aim was to investigate if regions of increased perfusion or tumor with restricted diffusion on the immediate post-operative MRI examination would be predictive of time to tumor progression in patients with high-grade gliomas. MATERIALS AND METHODS: Twenty-three patients with high-grade gliomas were retrospectively analyzed. We measured the perfusion at the resection area and evaluated the presence or absence of the restricted diffusion in residual tumor masses. The associations of the perfusion, diffusion and contrast enhancement (delayed static enhancement (DSE)) characteristics with time to tumor progression were statistically calculated. We also evaluated if the location of the tumor progression was concordant to the areas of the elevated perfusion, tumor type restricted diffusion and enhancement. RESULTS: Patients with >200 days to progression are more likely to have no elevated relative cerebral blood volume (rCBV) ratio (p = 0.0004), no tumor restriction (p = 0.024), and no DSE (p = 0.052). The elevated mean rCBV ratio (p<0.001) and tumor type restricted diffusion (p = 0.002) were significantly associated with a higher risk of progression. All cases with rCBV ratio of >1.5 progressed in 275 days or earlier. Tumors tended to progress at the area where patients with post-operative MRIs showed elevated perfusion (p = 0.006), tumor-type restricted diffusion (p = 0.005) and DSE (p = 0.008). CONCLUSIONS: Post-operative analysis of rCBV, tumor type restricted diffusion and enhancement characteristics are predictive of time to progression, risk of progression and where tumor progression is likely to occur.

The moderating role of social support for marital adjustment, depression, anxiety, and stress: Evidence from Pakistani working and nonworking women.

BACKGROUND: This study examined how social support moderates the prolongation of mental distress related to depression, anxiety, stress, and marital adjustment in working and nonworking women. The study aimed to reveal the relationship between social support and mental health issues associated with depression, anxiety, stress, and marital adjustment among females. METHODS: This research study is among the few studies performed in a Pakistani context and was conducted in 2017 to measure affective disorders among nonworking and working married females. Questionnaires were distributed among 500 targeted women, and valid responses were received from married working women in hospitals, banks, and multinational companies, and married nonworking women from residential areas of Islamabad and Rawalpindi, Pakistan. A cross-sectional design with purposive sampling was adapted for this research, and three scales were used to measure stress, anxiety, depression, social support, and marital adjustment and its social and cultural implications among the sampled population. RESULTS: Social support was positively and significantly associated with marital adjustment, although it showed a negative association with anxiety, depression, and stress in working and nonworking women; this finding reflects the better mental health of the study population. The findings proved that marital adjustment has a negative relation with depression and anxiety in married working and nonworking females. Social support acts as a moderator for marital cohesion, affection, stress, and depression, and the results reflected that nonworking women with higher marital cohesion and affection showed less stress and depression because of social support. LIMITATIONS: The findings of this sample cannot be generalized to the whole population as they are specific to the targeted respondents only. CONCLUSION: The study revealed that women's mental health is affected by psychological distress caused by depression, anxiety, stress, social and cultural norms, and their implications. Lower stress and depression lead to better mental health as ostensive social support may help to explain the relationship between depression, anxiety, and stress.

Cladophialophora Bantiana : A Rare Intracerebral Fungal Abscess-Case Series and Review of Literature.

Background Intracerebral Cladophialophora bantiana may carry up to a 70% mortality rate despite advances in surgical resection capabilities and the use of both systemic and intrathecal antifungal treatments. Objectives The authors examined a retrospective case series of two patients with intracerebral infection from the rare, neurotropic fungus Cladophialophora bantiana and conducted a literature review to evaluate optimal therapies. Patients/Methods At our institution, the patients' cases presented with raised intracranial features of headache, visual field cut, and/or memory loss, with a correspondingly wide variety of radiological differential diagnoses. It was the microbiological, histopathological, and genomic identification of C. bantiana that ensured targeted, individualized patient therapies. Results and Conclusions Successful treatment depends on obtaining a complete surgical resection, an accurate microbiological diagnoses for mold identification, and an effective long-term, personalized antifungal treatment. Close radiographic surveillance is necessary to ensure complete eradication of pheoid fungi.

Assessment of vascularity in glioblastoma and its implications on patient outcomes.

There is little data on why glioblastomas (GBM) hemorrhage and how it may affect patient outcomes. The aim of this study was to investigate the mechanisms of hemorrhage in glioblastoma by examining molecular and genetic features by immunohistochemistry (IHC) and mRNA expression profiles in association with imaging and clinical outcomes. An observational retrospective cohort analysis was performed on 43 FFPE GBM tissue samples. MR images were assessed for the presence of hemorrhage and extent of resection. Specimens were examined for CD34 and CD105 expression using IHC. Tumor mRNA expression profiles were analyzed for 92 genes related to angiogenesis and vascularity. Forty-three specimens were analyzed, and 20 showed signs of hemorrhage, 23 did not. The average OS for patients with GBM with hemorrhage was 19.12 months (95% CI 10.39-27.84), versus 13.85 months (95% CI 8.85-18.85) in those without hemorrhage (p > 0.05). Tumors that hemorrhaged had higher IHC staining for CD34 and CD105. mRNA expression analysis revealed tumor hemorrhage was associated with increased expression of HIF1α and MDK, and decreased expression of F3. Hemorrhage in GBM was not associated with worsened OS. Increased expression of angiogenic factors and increased CD34 and CD105 IHC staining in tumors with hemorrhage suggests that increased hypoxia-induced angiogenesis and vessel density may play a role in glioblastoma hemorrhage. Characterizing tumors that are prone to hemorrhage and mechanisms behind the development of these hemorrhages may provide insights that can lead to the development of targeted, individualized therapies for glioblastoma.

Effect of angiotensin converting enzyme inhibitor on glomerular hyperfiltration in patients with type 1 diabetes.

OBJECTIVE: To assess the effect of angiotensin converting enzyme inhibition on glomerular filtration rate (GFR) in normotensive patient with type 1 diabetes. METHODS: A two year non-placebo control prospective study was conducted after ethical approval at Diabetes Centre of Diabetic Association of Pakistan, a WHO collaborating centre in Karachi, Pakistan. All patients with type 1 diabetes visited the out-patients department from August 2009 till July 2011 and those who fulfilled the inclusion criteria were invited to participate. A total of 121 people aged ≥18 years and ≥ 5 years of diabetes were included. Pregnant and lactating woman and those aged <18 years were excluded. GFR was calculated by using CKD-EPI formula (eGFR) at baseline and after two year. On the basis of estimated GFR, patients at baseline were divided according to KDIGO classification of chronic kidney diseases into, hyperfiltration (eGFR ≥ 100 ml/min) and normal filtration group (eGFR < 100 ml/min). All subjects in hyperfiltration group received ACE inhibitor (treatment group) while patients with normal filtration did not receive ACE inhibitor (control group). RESULTS: Fifty two patients (43%) were in the treatment and sixty nine (57%) were in the control group. At baseline eGFR, systolic and diastolic blood pressures between groups were non-significantly different. After two years, compared to baseline, eGFR of the treatment group declined and the control group increased significantly. No significant difference in systolic while diastolic blood pressure of the treatment group increased significantly after two years compared to baseline. In contrast both systolic and diastolic blood pressure of control group increased significantly after two years compared to their baseline values. CONCLUSION: Present study demonstrated that initiation of ACEI in hyperfiltration stage declined GFR and keep blood pressure within normal range.

Chronic kidney disease hotspots in developing countries in South Asia.

In many developing countries in the South Asian region, screening for chronic diseases in the community has shown a widely varying prevalence. However, certain geographical regions have shown a high prevalence of chronic kidney disease (CKD) of unknown etiology. This predominantly affects the young and middle-aged population with a lower socioeconomic status. Here, we describe the hotspots of CKD of undiagnosed etiology in South Asian countries including the North, Central and Eastern provinces of Sri Lanka and the coastal region of the state of Andhra Pradesh in India. Screening of these populations has revealed cases of CKD in various stages. Race has also been shown to be a factor, with a much lower prevalence of CKD in whites compared to Asians, which could be related to the known influence of ethnicity on CKD development as well as environmental factors. The difference between developed and developing nations is most stark in the realm of healthcare, which translates into CKD hotspots in many regions of South Asian countries. Additionally, the burden of CKD stage G5 remains unknown due to the lack of registry reports, poor access to healthcare and lack of an organized chronic disease management program. The population receiving various forms of renal replacement therapy has dramatically increased in the last decade due to better access to point of care, despite the disproportionate increase in nephrology manpower. In this article we will discuss the nephrology care provided in various countries in South Asia, including India, Bangladesh, Pakistan, Nepal, Bhutan, Sri Lanka and Afghanistan.

Biaxial mechanical properties of the human thoracic and abdominal aorta, common carotid, subclavian, renal and common iliac arteries.

The biomechanics of large- and medium-sized arteries influence the pathophysiology of arterial disease and the response to therapeutic interventions. However, a comprehensive comparative analysis of human arterial biaxial mechanical properties has not yet been reported. Planar biaxial extension was used to establish the passive mechanical properties of human thoracic (TA, [Formula: see text]) and abdominal (AA, [Formula: see text]) aorta, common carotid (CCA, [Formula: see text]), subclavian (SA, [Formula: see text]), renal (RA, [Formula: see text]) and common iliac (CIA, [Formula: see text]) arteries from 11 deceased subjects ([Formula: see text] years old). Histological evaluation determined the structure of each specimen. Experimental data were used to determine constitutive parameters for a structurally motivated nonlinear anisotropic constitutive model. All arteries demonstrated appreciable anisotropy and large nonlinear deformations. Most CCA, SA, TA, AA and CIA specimens were stiffer longitudinally, while most RAs were stiffer circumferentially. A switch in anisotropy was occasionally demonstrated for all arteries. The CCA was the most compliant, least anisotropic and least frequently diseased of all arteries, while the CIA and AA were the stiffest and the most diseased. The severity of atherosclerosis correlated with age, but was not affected by laterality. Elastin fibers in the aorta, SA and CCA were uniformly and mostly circumferentially distributed throughout the media, while in the RA and CIA, elastin was primarily axially aligned and concentrated in the external elastic lamina. Constitutive modeling provided good fits to the experimental data for most arteries. Biomechanical and architectural features of major arteries differ depending on location and functional environment. A better understanding of localized arterial mechanical properties may support the development of site-specific treatment modalities for arterial disease.

Passive biaxial mechanical properties and in vivo axial pre-stretch of the diseased human femoropopliteal and tibial arteries.

Surgical and interventional therapies for atherosclerotic lesions of the infrainguinal arteries are notorious for high rates of failure. Frequently, this leads to expensive reinterventions, return of disabling symptoms or limb loss. Interaction between the artery and repair material likely plays an important role in reconstruction failure, but data describing the mechanical properties and functional characteristics of human femoropopliteal and tibial arteries are currently not available. Diseased superficial femoral (SFA, n = 10), popliteal (PA, n = 8) and tibial arteries (TA, n = 3) from 10 patients with critical limb ischemia were tested to determine passive mechanical properties using planar biaxial extension. All specimens exhibited large nonlinear deformations and anisotropy. Under equibiaxial loading, all arteries were stiffer in the circumferential direction than in the longitudinal direction. Anisotropy and longitudinal compliance decreased distally, but circumferential compliance increased, possibly to maintain a homeostatic multiaxial stress state. Constitutive parameters for a four-fiber family invariant-based model were determined for all tissues to calculate in vivo axial pre-stretch that allows the artery to function in the most energy efficient manner while also preventing buckling during extremity flexion. Calculated axial pre-stretch was found to decrease with age, disease severity and more distal arterial location. Histological analysis of the femoropopliteal artery demonstrated a distinct sub-adventitial layer of longitudinal elastin fibers that appeared thicker in healthier arteries. The femoropopliteal artery characteristics and properties determined in this study may assist in devising better diagnostic and treatment modalities for patients with peripheral arterial disease.

Multifocal histologically malignant Epstein-Barr virus-associated smooth muscle tumor in a pediatric transplant patient with an indolent course.

Epstein-Barr virus-associated smooth muscle tumors (EBV-SMTs) are rare lesions that occur in immunocompromised patients. Dural involvement appears to be less common in organ transplant recipients than in HIV patients. Due to the paucity of reported cases following organ transplantation, the natural history of these lesions is unclear. We describe an 8-year-old female who presented with adrenal, small bowel, and intracranial tumors 6 years following renal transplantation. Histopathological analysis revealed a highly cellular, mitotically active, smooth muscle neoplasm without necrosis. The tumor stained diffusely for smooth muscle actin and myosin. In situ hybridization for EBV-encoded RNA was diffusely positive. Following gross total resection, antiviral therapy, and a reduction in immunosuppression, the patient is tumor-free at 3 years follow-up. In patients with compromised immune systems, it is important to recognize this unique form of SMT because, even when there are multiple lesions, the prognosis may be excellent.

Effects of carotid artery stenting on arterial geometry.

BACKGROUND: The role of carotid artery stenting (CAS) for the treatment of carotid artery disease continues to evolve, despite higher stroke and restenosis risks for CAS compared with conventional open endarterectomy. Understanding the effects of CAS on arterial geometry, which strongly influence hemodynamics and wall mechanics, can assist in better stratifying the inherent risk of CAS to individual patients. STUDY DESIGN: Fifteen consecutive patients undergoing CAS had pre- and post-stenting CT angiograms. These images were used to reconstruct the 3-dimensional geometries of the bilateral carotid arteries from their origin to the skull base. Quantitative assessment of the carotid bifurcation angle, cross-sectional area, tortuosity and artery length, were compared pre- and post-stenting. Plaque volume and calcification were also measured. Mathematical models were devised to determine the mechanisms of CAS-induced geometric changes, and their mechanical and hemodynamic significances. RESULTS: Major and moderate changes in arterial tortuosity and elongation were seen in 5 (33%) patients. Characteristics most associated with the development of CAS-induced geometric changes were stenoses located in the internal carotid artery distal to the carotid bulb, circumferential distribution of plaque, and plaque calcification. Modeling did not demonstrate substantial alterations in wall shear stress due to geometric changes, but did show considerable increases in arterial wall axial stress. CONCLUSIONS: Carotid artery stenting can produce geometric changes to the artery that promote favorable conditions for complications and recurrent disease. Patients with circumferential, highly calcified plaques that are located relatively distal in the internal carotid artery are most likely to have post-stenting geometric changes.

Metastases from nested variant urothelial carcinoma of the urinary bladder in pancreatic allograft mimicking graft rejection.

UNLABELLED: While not an uncommon tumor, urothelial carcinoma of the urinary bladder is rare in bladders draining pancreatic allografts. A case of urothelial carcinoma directly involving a pancreatic allograft with metastasis that occurred in a 49-year-old pancreas and kidney transplant recipient is described. Her initial clinical presentation and findings of CT scan of the abdomen suggested pancreatitis with features worrisome for rejection. A biopsy of her pancreatic allograft contained poorly differentiated carcinoma and cystoscopic biopsy disclosed an invasive high grade urothelial carcinoma arising in the background of extensive urothelial carcinoma in situ. Exploratory laparotomy revealed that the tumor invaded the right ovary and fallopian tube, cecum, and allograft with extensive retroperitoneal involvement. She underwent en bloc resection of distal ileum and cecum, resection of transplant pancreas, partial cystectomy, ileocolostomy anastomosis, and right salpingo-oophorectomy. Postoperatively, the patient was treated with four cycles of carboplatin and gemcitabine. She ultimately succumbed to her disease approximately 1 year after diagnosis. This case should alert physicians and radiologists to be aware of atypical presentation of urothelial carcinoma in bladder-drained pancreas grafts, the aggressiveness of such lesions, and the need for early biopsy to avoid diagnostic confusion with rejection. KEYWORDS: Bladder cancer; Nested variant of urothelial carcinoma; Pancreas and kidney transplantation.

Efficiency of plant growth promoting rhizobacteria isolated from sand dunes of Chennai coastal area.

Plant Growth Promoting Rhizobacteria (PGPR) are beneficial bacteria that colonize the plant root and enhance the plant growth. The use of PGPR is steadily increasing in agriculture and offers an attractive way to replace chemical fertilizers, pesticides and supplements. In the present study, PGPR were isolated from 18 different rhizosphere soil samples of coastal sand dune plants, belonging to the genus Ipomoea sp. collected from the Chennai coastal area. For isolation of bacteria from soil samples, pour plate technique was followed. The rhizobacterial population was ranged from 4.4 x 10(6)-7.5 x 10(7) CFU g(-1). From that, 46 morphologically different bacterial strains were isolated. Among 46, 18 strains exhibited the production of Indole Acetic Acid. (IAA). When screened for phosphate solubilzing activity, six strains showed maximum activity. All these selected six strains were screened for seed germination among which these two strains (AMET1136 and AMET 1148) showed remarkable increase in the seed germination of black gram and green gram. For plant growth promotion, three types of treatments namely, seed bacterization, soil drenching and mixed (seed+soil) were carried out to check the potential of these two strains. Among that one strain which was identified as Pseudomonas sp. AMET1148 showed remarkable and significant increase in shoot length and root length of the tested plants. The study concluded that PGPR from coastal sand dund plants can be developed as plant growth promoters in agricultural crops.

Comparative analysis of the biaxial mechanical behavior of carotid wall tissue and biological and synthetic materials used for carotid patch angioplasty.

Patch angioplasty is the most common technique used for the performance of carotid endarterectomy. A large number of patching materials are available for use while new materials are being continuously developed. Surprisingly little is known about the mechanical properties of these materials and how these properties compare with those of the carotid artery wall. Mismatch of the mechanical properties can produce mechanical and hemodynamic effects that may compromise the long-term patency of the endarterectomized arterial segment. The aim of this paper was to systematically evaluate and compare the biaxial mechanical behavior of the most commonly used patching materials. We compared PTFE (n = 1), Dacron (n = 2), bovine pericardium (n = 10), autogenous greater saphenous vein (n = 10), and autogenous external jugular vein (n = 9) with the wall of the common carotid artery (n = 18). All patching materials were found to be significantly stiffer than the carotid wall in both the longitudinal and circumferential directions. Synthetic patches demonstrated the most mismatch in stiffness values and vein patches the least mismatch in stiffness values compared to those of the native carotid artery. All biological materials, including the carotid artery, demonstrated substantial nonlinearity, anisotropy, and variability; however, the behavior of biological and biologically-derived patches was both qualitatively and quantitatively different from the behavior of the carotid wall. The majority of carotid arteries tested were stiffer in the circumferential direction, while the opposite anisotropy was observed for all types of vein patches and bovine pericardium. The rates of increase in the nonlinear stiffness over the physiological stress range were also different for the carotid and patching materials. Several carotid wall samples exhibited reverse anisotropy compared to the average behavior of the carotid tissue. A similar characteristic was observed for two of 19 vein patches. The obtained results quantify, for the first time, significant mechanical dissimilarity of the currently available patching materials and the carotid artery. The results can be used as guidance for designing more efficient patches with mechanical properties resembling those of the carotid wall. The presented systematic comparative mechanical analysis of the existing patching materials provides valuable information for patch selection in the daily practice of carotid surgery and can be used in future clinical studies comparing the efficacy of different patches in the performance of carotid endarterectomy.

Teratoma with malignant transformation: a case report with pathological, cytogenetic, and immunohistochemistry analysis.

Background. Teratoma with malignant transformation (TMT) is rare and most commonly encountered in adult patient with germ cell tumor (GCT). Method. We report a rare case of testicular teratoma with metastatic TMT/embryonal rhabdomyosarcoma (ERMS). A 44-year-old man underwent right orchiectomy which revealed a malignant teratoma, he subsequently had right pneumonectomy with two pulmonary masses containing a high-grade embryonal rhabdomyosarcoma. The patient developed liver metastasis three months after initial diagnosis. He was treated with a chemotherapy regimen with vincristine, dactinomycin, and cyclophosphamide (VAC) alternating with vincristine and irinotecan (VI) with complete resolution of his liver lesion. The tumors were examined with a battery of cytogenetic, immunohistochemical, and molecular assays. Results. The malignant cells were immunohistochemically positive for desmin, myogenin, and MyoD1. Molecular cytogenetics of embryonal rhabdomyosarcoma tissue revealed the presence of i(12p). The tumor expressed high level of TOPO2A, TOPO1, MRP1, MGMT, BCRP, ERCC1, RRM1, and TS. Conclusion. The activity of topoisomerase inhibitors and the potential usefulness of topoisomerase expression as biomarkers should be further tested in aprospective study.

Protective role of Phyllantus niruri extract in doxorubicin-induced myocardial toxicity in rats.

OBJECTIVES: To investigate the effect of the aqueous extract of Phyllanthus niruri (Aq.E.PN) against doxorubicin (Dox)-induced myocardial toxicity in rats. MATERIALS AND METHODS: Cardiotoxicity was produced by Dox administration (15 mg/kg for 2 weeks). Aq.E PN (200 mg/kg, orally) was administered as pretreatment for 2 weeks alternated with Dox for the next 2 weeks. The general observations, mortality, histopathology, biomarker enzymes like lactate dehydrogenase (LDH), creatinine phosphokinase (CPK) and alkaline phosphatase, diagnostic enzyme markers like aspartate aminotransferase (AST) and alanine aminotransferase (ALT), and antioxidants such as glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) were monitored after 3 weeks of the last dose. RESULTS: Pretreatment with the Aq.E.PN significantly (P < 0.01) protected the myocardium from the toxic effects of Dox by reducing the elevated level of biomarker and diagnostic enzymes like LDH, CPK, AST and ALT to the normal levels. Aq.E PN increased the GSH, SOD and CAT levels and decreased the MDA levels in cardiac tissue. Administration of Dox caused cardiomyopathy associated with an antioxidant deficiency. CONCLUSION: These results suggest a cardioprotective effect of P. niruri due to its antioxidant properties.