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Volumen 8, Asunto 5 (2017)

Caso de estudio

Antioxidant Modulation of Hematological Toxicity during Chemotherapy for Breast Cancer

Hojouj Mohammad, Bondarenko I, Zavizion V, Artemnko M, Soloviova N, Bondarenko Y, Dmytrenko K and Urzhumova N

Side effects of anticancer drugs seriously limit the achievement of the maximum therapeutic effect of the most cytostatic. One of the pathophysiological bases of side effects is the ability of cytotoxic agents to intensify the freeradical processes and the consequent lipid peroxidation (LPO) in the cell membranes of various organs. When the antitumor treatment is conducted, the antioxidant enzyme deficiency increases, there is the depletion of nonenzymatic and enzymatic mechanisms of oxidation protection units, resulting in a reduction of organism resistance and damage to vital organs and systems. In this connection it is important to study the possibility of correction of violations occurring in cancer patients with drugs with antioxidant action type.

Reporte de un caso

Primary renal myxofibrosarcoma in a woman: A case report and literaturereview

Sung Han Kim, Yoon Seok Suh, Jung Kwon Kim, Weon Seo Park, Seog Yun Park, Ji Hyeon Lee, Sun Ho Kim, Jae Young Joung, Ho Kyung Seo, Kang Hyun Lee, and Jinsoo Chung

A 45-year-old previously healthy woman presented to our hospital with a right abdominal mass. Abdominal computed tomography (CT), magnetic resonance imaging, and bone scanning revealed a 15-×10-×14-cm, welldelineated, retroperitoneal tumor originating from the right kidney. No metastases detected. The patient underwent successful extirpation of the renal tumor. The tumor showed 50% necrosis without perirenal fat infiltration, and it was diagnosed as a high-grade (grade 3) myxofibrosarcoma without nodal positivity, according to the French Federation of Cancer Centers Sarcoma (FNCLCC) grading system. Tumor immunohistochemical staining revealed positive staining for CD34, Ki67, smooth muscle actin (SMA), and cluster of differentiation 68 (CD68), and negative staining for S100 protein, desmin, mast/stem cell growth factor receptor (c-kit), and melanoma marker antibody (HMB45). Three months post-surgery, follow-up CT revealed no new abdominal metastasis, and the patient is currently receiving routine follow-up without any additional systemic therapy. Myxofibrosarcoma of the kidney is an uncommon soft tissue tumor, and radical surgery is the treatment of choice. Long-term follow-up is recommended because of the tumor’s aggressive invasiveness and potential for distant metastasis.

Mini reseña

Specific Agonists and Antagonists of Serotonergic Receptors in theTreatment of Cognitive Symptoms in Alzheimer's Disease

Felix-Martin Werner

In Alzheimer’s disease, decreasing activity of acetylcholine and GABA in the hippocampus and prefrontal cortex are combined with cognitive deficits and with the formation of beta-amyloid. Neurotransmitter alterations in these brain regions are described, while a neurotransmitter imbalance with hypoactivity of muscarinic cholinergic, serotonergic and GABAergic neurons and hyperactivity of noradrenergic and glutamatergic neurons can be found. Serotonin including some specific receptors play an essential role in cognitive symptoms in Alzheimer’s disease. Neural networks in the hippocampus and prefrontal cortex are described. Animal experiments and clinical trials about the pro-cognitive effect of 5-HT4 and 5HT7 agonists and of 5-HT3 and 5-HT6 antagonists are mentioned. The question should be investigated, whether a hybrid of a GABAA agonist and an NMDA antagonist is of a therapeutic value in mild Alzheimer’s disease.

Artículo de investigación

Modulation of Pancreatic β-Cells and Antioxidant Status by Cinnamon in Type 2 Diabetic Rats

Noor Fatima, Areeba Khaleeq, Shahrukh Momin, Rizwana S Waraich, Saima Khaliq and Rahman M Hafizur

The effect of Cinnamomum cassia was investigated in a non-obese type 2 diabetic rat model to explore possible cellular mechanism(s) of its antidiabetic activity. Non-obese type 2 diabetes was developed in rats by injecting 60 mg/kg streptozotocin (STZ) along with 120 mg/kg nicotinamide (NA) in adult Wistar rats. Type 2 diabetes was confirmed after 14 days of STZ-NA induction. Diabetic rats were treated with cinnamon extract at 250 mg/kg (Cn250) or 500 mg/kg dose (Cn500) and the positive control, glibenclamide (5 mg/kg) for 28 days. After treatment, blood glucose, serum insulin, HbA1c and antioxidant status were measured. Additionally, insulin and glucagon immunostaining was performed in pancreatic sections. Moderate hyperglycemia and β-cells dysfunction was found in this diabetic model rats. Interestingly, cinnamon extract treatment lowered the elevated blood glucose (Cn250: 269.8 ± 18.5 mg/dl vs. 322.5 ± 12.5 mg/dl, p<0.01; Cn500: 195.2 ± 22.5 mg/dl vs. 322.5 ± 12.5 mg/dl, p<0.001) and enhanced serum insulin levels (Cn250: 0.28 ± 0.032 ng/ml vs. 0.195 ± 0.03 ng/ml; Cn500: 0.45 ± 0.035 ng/ml vs. 0.195 ± 0.03 ng/ml, p<0.001) in a dose-dependent manner. In diabetic rats, a drastic decrease of β-cell function was observed while cinnamon extract treatment elevated the β-cell function significantly (p<0.05) in Cn500 treated group. Qualitative and quantitative improvement of pancreatic β-cell morphology was found in cinnamon-treated rats. Total antioxidant status was improved by cinnamon extract suggesting its antioxidant potential in Cn500 dose significantly (1.83 ± 0.05 mmol/L vs. 1.49 ± 0.09 mmol/L, p<0.05). Glibenclamide showed similar action to that of 500 mg/kg cinnamon in all the assays. Collectively, the data suggest that cinnamon exerts antidiabetic activity by increasing insulin secretion, modulating β-cell function, and improving antioxidant status in non-obese type 2 diabetic model rats.

Artículo de investigación

Co-upregulation of Transforming Growth Factor Beta-1 and Nitric Oxide Synthase in Keloid by comparison to normal human skin-A possible role for TGFβ1 and NOS in pathogenesis of keloid

Seham A Abd El-Aleem, Soha Abdelwahab and Noura Mohamed Saber Osman

Keloid disease is a benign but progressive form of abnormal wound healing associated with skin fibrosis and can cause a major functional disability and morbidity. TGF beta (TGFβ) and Nitric Oxide (NO) are active biomarkers known to regulate phases of wound healing and have been implicated in pathogenesis of fibrotic disease. There are three isoforms of TGFβ (1, 2 and 3), TGFβ1 and 3 have a crucial role in fibrosis, with TGFβ1 profibrotic and TGFβ3 antifibrotic. NO is produced by Nitric Oxide Synthase (NOS) which exist in three isoforms, inducible NOS (iNOS), endothelial NOS (ecNOS) and neuronal NOS (nNOS). TGFβ isoforms and NO were found to be associated with fibrotic disorders affecting the skin. We hypothesis that the interaction between TGFβ and NO in keloid could promote the excessive collagen deposition associated with this disorder. Using immunohistochemistry, we investigated the profile of TGFβ isoforms (TGFβ1, 3) and NOS isoforms (iNOS and ecNOS) in keloid tissues and normal human skin. The cellular distribution of all the isoforms were studied and the protein levels were assessed by using H-Scoring and Image J Scoring systems. TGFβ1 showed wide cellular distribution in keloid both in the epidermal and dermal cells. There was significant upregulation (P<0.0001) by comparison to normal skin. TGFβ3 showed limited expression in keloid and there was significant downregulation (P<0.03). iNOS and ecNOS showed significant upregulation in keloid by comparison to normal skin (P<0.01 and P<0.02) respectively. Interestingly, iNOS was expressed in the basal epidermal layer and in dermal connective tissue cells while ecNOS was solely expressed in vascular endothelial lining. Although it is documented that TGFβ has a negative feedback effect on iNOS, we have shown co-upregulation of TGFβ1 and iNOS in keloids. Thus, in keloid NO is as important as the profibrotic growth factor TGFβ1 and both could be working in coordination. Moreover, the lack of effective therapy for keloid could be because most of the therapeutic regimen target one factor while the other still in action. In conclusion, understanding the actions of TGFβ and NOS in keloid disease could lead to the development of clinically useful combined anti-fibrotic agents.

Artículo de revisión

Osteosarcoma in Dogs: Diagnosis and Treatment - A Literature Review

Paula de Sanctis, Brunno Felipe Ramos Caetano, Luis Mauricio Montoya Flórez, Valéria Barsosa de Souza, Willian Fernando Zambuzzi and Noeme Sousa Rocha

Among primary bone tumors, osteosarcoma (OSA) is the most diagnosed in dogs. OSA is a highly aggressive tumor and metastatic spread to the lungs contributes to the poor prognosis. Surgery followed by adjuvant chemotherapy and radiation therapy is the current treatment of choice for this disease. However, surgery is not applied in all cases because dog owners disagree with partial or total amputation of the limb. Due to the aggressiveness of the disease, this review aims to gather information about the biological bases of the OSA, to discuss its diagnosis and treatment as well as to serve as an instrument in comparative oncological research encouraging effective diagnostic and therapeutic approaches to be improved and discovered.

Artículo de investigación

Correlation between Epiretinal Membrane Bridging, Visual Acuity and Central Macular Thickness

Jelena Paovic, Predrag Paovic and Anka Stanojevic Paovic

Epiretinal membrane or macular pucker is avascular, fibrocellular membrane that develops on the inner surface of the retina that can result in various stages of macular dysfunction. Fine epiretinal membranes lead to minimal visual loss, whilst epiretinal membranes (that may or may not bridge the fovea) are, in their more severe stages, accompanied by macular edema and image distortion that is caused by pronounced tractional membranes and perifoveal capillary leakage. Macular edema and its’ type, as well as epiretinal membrane bridging the fovea can precisely be defined and monitored via optical coherence tomography. This study included a total of 138 patients (188 eyes) with epiretinal membranes (95 on the right and 93 on the left eye). Macular edema was present in 144 eyes with, and 69 eyes without, epiretinal membranes. Data obtained for both eyes indicates that upon analysis number of patients in both examined groups (epiretinal membrane bridged and did not bridge the fovea) increases exponentially with increased visual acuity, and suggests that there is no considerable difference in distribution of visual acuity with regards to patients in both examined groups. This data also indicates that patients with the worst central macular thickness (>500μ) are represented only in the group of patients where epiretinal membrane had bridged the fovea, but that in both examined groups there is a difference in prevalence of patients with central macular thickness of 400 to 499μ (more common in the group that did, than in the group that did not, bridge the fovea). Hence, there exists a relationship between epiretinal membrane that bridges the fovea and central macular thickness. Aim of this study is to determine the extent in which epiretinal membrane bridging or not bridging the fovea influences visual acuity and to determine the relationship between them; central macular thickness; and visual acuity.

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