The influence of uric acid treatments on liver glutathione system prevent oxidative damages in experimental autoimmune encephalomyelitis mice

Recently we reported that antioxidant system in brain and spinal cord in experimental autoimmune encephalomyelitis (EAE) mice is mainly affected at early stages of the disease [M. Zargari, A. Allameh, M.H. Sanati, T. Tiraihi, S.H. Lavasani, O. Emadyan, Relationship between the clinical scoring and demyelination in central nervous system with total antioxidant capacity of plasma during experimental autoimmune encephalomyelitis development in mice, Neurosci. Lett. 412 (2007), 24–28]. The aim of the present study was to investigate the role of uric acid (UA) on antioxidant system in liver and plasma of EAE mice. EAE was induced in C57/BL6 mice (n = 60), followed by i.p. administration of UA (10 mg/kg BW) in 30 mice at three distinct clinical stages (A: prior to onset, B: after onset, C: after development of EAE). Livers were removed and processed for measurement of lipid peroxidation products, reduced glutathione (GSH), and glutathione S-transferase (GST) and total antioxidant capacity of plasma (FRAP). The results showed that lipid peroxidation products in liver of EAE mice was increased significantly (∼85%) as compared to normal. UA administration to EAE mice caused a significant suppression of liver lipid peroxidation products (∼45%) at early stages (A and B). There was an inverse relationship between lipid peroxidation and cellular GSH in liver. GSH was significantly depleted in mice liver during the EAE progression, but it was recovered (∼29%) when UA was injected before the onset of the disease (groups A and B). Plasma total antioxidant capacity was significantly decreased during the development of EAE, however it was subsided in mice treated with UA as compared to the corresponding controls (21%) in groups A and B. Elevated liver GST as a result of EAE induction was reversed in mice treated with UA particularly in groups A and B. These results indicate that hepatic glutathione system, particularly GST plays a major role in modulation of oxidative damages to central nervous system (CNS) during EAE induction. The positive response of antioxidant system to UA administration in EAE mice was corroborated with improvement of clinical manifestation of the animals.     

Requirements for the development of IL-4-producing T cells during intestinal nematode infections: what it takes to make a Th2 cell in vivo

Summary: Components of the type 2 immune response may mediate host protection against both helminthic parasites and harmful allergic responses. A central player in this response is the T‐helper 2 (Th2) effector cell, which produces interleukin (IL)‐4, IL‐5, IL‐13, and other Th2 cytokines during the primary and memory response. Specific aspects of the parasite that trigger Th2‐cell differentiation are not yet defined. Furthermore, the cell types and cell surface and secreted molecules that provide the immune milieu required for the development of Th2 effector cells and also Th2 memory cells are not well understood. They will probably vary with the particular helminth or other antigen inducing the Th2 response. We have used third stage larvae of intestinal nematode parasites as adjuvants to promote naïve nonparasite antigen‐specific T cells to differentiate into Th2 cells. This model system avoids possible parasite antigen‐specific T‐cell clones or cross‐reactive memory T cells that may preferentially differentiate into Th2 effector cells during the course of infection and confound the stereotypical components of parasite‐induced Th2 cell differentiation. We have found that these parasites have a potent adjuvant effect and have used our model system to begin to investigate the events that lead to the development of polarized Th2 cells in vivo.     

Association between the DRD2 A1 allele and opium addiction in the Iranian population.

Dysfunction of the central dopaminergic neurotransmission has been suggested to play an important role in the etiology of certain neuropsychiatric disorders such as drug abuse. It has been shown that the dopamine D2 receptor (DRD2) gene dysfunction is associated with multi-drug addiction. Addiction to opium is the most common form of drug abuse in Iran. We studied the allelic association between DRD2 Taq I A polymorphism in 100 opium-dependent Iranian patients and 130 unrelated controls. A 310 bp (base pair) region surrounding Taq I site at the DRD2 locus was amplified by polymerase chain reaction (PCR) and the PCR product was incubated with Taq I restriction enzyme. The A1 allele remained intact while the A2 allele was cut. Significant association was observed between A1 allele and addiction in the patients group (P < 0.0001). Moreover, the frequency of A1A1 genotype was significantly higher in opium users than controls (P < 0.0001). Our result indicates that DRD2 might be involved in the pathophysiology of opium addiction.     

GJB2 mutations: passage through Iran

Hereditary hearing loss (HHL) is a very common disorder. When inherited in an autosomal recessive manner, it typically presents as an isolated finding. Interestingly and unexpectedly, in spite of extreme heterogeneity, mutations in one gene, GJB2, are the most common cause of congenital severe-to-profound deafness in many different populations. In this study, we assessed the contributions made by GJB2 mutations and chromosome 13 g.1777179_2085947del (the deletion more commonly known as del (GJB6-D13S1830) that includes a portion of GJB6 and is hereafter called Delta(GJB6-D13S1830)) to the autosomal recessive non-syndromic deafness (ARNSD) genetic load in Iran. Probands from 664 different nuclear families were investigated. GJB2-related deafness was found in 111 families (16.7%). The carrier frequency of the 35delG mutation showed a geographic variation that is supported by studies in neighboring countries. Delta(GJB6-D13S1830) was not found. Our prevalence data for GJB2-related deafness reveal a geographic pattern that mirrors the south-to-north European gradient and supports a founder effect in southeastern Europe.     

Bone mineral density is related to blood pressure in men

The aim of this study was to determine the relationships between bone mineral density (BMD) and blood pressure in 214 men, age 20–76. BMD measurements were done by dual X‐ray absorptiometry using a Lunar DPXMD densitometer at the lumbar spine (L2–L4) and different femoral regions. Systolic (SBP) and diastolic (DBP) blood pressure were measured using an MPC‐350 sphygmomanometer. Physicians gathered demographic data and participants' dietary intake of calcium were determined by using food frequency questionnaires. After adjusting for age, body mass index, dietary calcium, and exercise history, multiple linear regression models showed that DBP was negatively related to femoral neck BMD (β = ?0.145, P = 0.032) and just shy of significant association with femoral neck BMC (β = ?0.114, P = 0.079). SBP was correlated with femoral neck (r = ?0.171, P = 0.012) and Ward's (r = ?0.186, P = 0.006) BMD but not after adjusting for possible confounders. Further studies are needed to determine whether elevated blood pressure is causally related to the development of low bone mass. Am. J. Hum. Biol. 16:168–171, 2004. © 2004 Wiley‐Liss, Inc.     

Lipid peroxidation and antioxidant status in human cervical carcinoma

Reactive oxygen species (ROS), represented by superoxide, hydrogen peroxide and hydroxyl radicals, have been implicated in many diseases including cancer. ROS have been known to play an important role in the initiation and promotion of multistep carcinogenesis. The cellular antioxidants play a crucial role in protection against neoplastic disease. However, very little is known about the antioxidant defense in cervical carcinoma. This is addressed in the present study. Lipid peroxides, glutathione content and the activities of antioxidant enzymes, together with vitamin C and E content, were estimated in patients who had carcinoma of the cervix, and the values were compared with those of normal women. The results showed a remarkable reduction in the content of glutathione, vitamin E and C. Activities of glutathione peroxidase and superoxide dismutase were also reduced in cervical cancer compared to normal controls (P < 0.001). This reduction was more marked in late stages (III, IV) than in early stages (I, II) (P < 0.001). Glutathione was reduced more in poorly differentiated tumors (grade III) than in well and moderately differentiated ones (grade I, II) (P < 0.05). Levels of lipid peroxides were found to be significantly higher in malignant than in normal tissue samples and their levels were correlated with advanced clinical stage (P < 0.001). Our results suggest impaired antioxidant status in carcinoma of the cervix. This impairment is related to tumor progression.     

PAN-811 provides neuroprotection against glutamate toxicity by suppressing activation of JNK and p38 MAPK

In an earlier study, we demonstrated that PAN-811 (3-aminopyridine-2-carboxaldehyde thiosemicarbazone), a novel neuroprotectant, provides protection against glutamate, staurosporine, veratridine, or hypoxia/hypoglycemia toxicities in primary cortical neuronal cultures by upregulating Bcl-2 expression [R.-W. Chen, C. Yao, X.C. Lu, Z.-G. Jiang, R. Whipple, Z. Liao, H.A. Ghanbari, B. Almassian, F.C. Tortella, J.R. Dave. PAN-811 (3-aminopyridine-2-carboxaldehyde thiosemicarbazone), a novel neuroprotectant, elicits its function in primary neuronal cultures by upregulating Bcl-2 expression. Neuroscience 135 (2005) 191–201]. Both JNK (c-Jun N-terminal kinase) and p38 MAP (mitogen-activated protein) kinase activation have a direct inhibitory action on Bcl-2 by phosphorylation. In the present study, we continued to explore the mechanism of PAN-811 neuroprotection. Our results indicate that treatment of cultured cortical neurons with glutamate (100 μM) induces phosphorylation of both JNK and p38 MAPK. Specifically, pretreatment of neurons with 10 μM PAN-811 (an optimal neuroprotective concentration) for 1 h, 4 h, or 24 h significantly suppresses glutamate-mediated activation of both JNK and p38 MAPK. Furthermore, the p38 MAPK-specific inhibitor SB203580 and the JNK-specific inhibitor SP600125 prevented glutamate-induced neuronal death in these primary cultures. Our results demonstrate that glutamate-induced phosphorylation of JNK and p38 MAPK is suppressed by PAN-811, which might contribute to Bcl-2 upregulation and PAN-811 neuroprotection.     

Pathologic study and clinical significance of Hürthle cell papillary thyroid carcinoma.

Hürthle cell papillary thyroid carcinoma is a variant of papillary thyroid carcinoma (PTC). Its pathologic and clinical significance has not been well documented. The authors studied the relative incidence of Hürthle cell PTC and the relationship of Hürthle cell PTC to other variants of thyroid carcinoma. Three hundred eighty consecutive cases of thyroid carcinoma were reviewed to identify cases with focal or extensive areas of Hürthle cell PTC, classic PTC, Hürthle cell carcinoma (ie, non-Hürthle cell PTC), and follicular carcinoma. In addition, the status of lymphoid infiltrate in the tumor, stromal invasion with desmoplastic reaction, vascular invasion, and distant and lymph node metastasis were noted by microscopic examination, review of clinical charts, or both. A total of 24 (HCs) and 42 PTCs with Hürthle cells were identified. The latter category was divided into pure Hürthle cell PTC or extensive Hürthle cell (HPTC) (28 cases) and PTC or Hürthle cell carcinoma with focal areas of Hürthle cell PTC (14 cases). The Hürthle cell PTC/Hürthle cell carcinoma ratio was lower than that of PTC/follicular carcinoma (39:289) (P = 0.001). Follicular or solid structures were present in all HPTCs. HPTCs were associated with frequent stromal intrathyroid and extrathyroid invasion, but they tended to have a lower rate of lymph node metastasis (8/28) compared with classic PTC with stromal invasion (108:200) (P = 0.12) and a lower rate of distant metastasis (2:28) compared with Hürthle cell carcinoma (15:24) (P = 0.02) or follicular carcinoma (13:39) (P = 0.04). Warthin-like Hürthle cell PTC (10 cases) was associated with extrathyroid invasion in five cases. In Hürthle cell PTC associated with tall cell variant (10 cases), areas of gradual transition between Hürthle cell PTC and tall cell variant were identified. The latter variant showed the highest rate of extrathyroid stromal and vascular invasion with distant metastasis and patient death compared with all Hürthle cell PTCs and classic PTCs. In conclusion, Hürthle cell PTC is frequently associated with tall cell variant. It has a higher potential for extrathyroid invasion than classic PTC and has vascular invasion and distant metastasis characteristics intermediate between those of classic PTC and Hürthle cell carcinoma with or follicular carcinoma. Hürthle cell PTC tends to show a greater likelihood of extrathyroid invasion when associated with Warthin-like features and tall cell variant PTC, and higher vascular invasion and distant metastasis when associated with tall cell variant.     

A report of pregnancy following ICSI in one of two sisters with familiar primary ciliary dyskinesia

Primary ciliary dyskinesia (PCD) is a disorder of structure and function of motor ciliary and dyskinetic activity of ciliary in the fallopian tubes of affected women and could lead to infertility in some cases. In vitro fertilisation (IVF) is a choice of treatment in infertile women with PCD, which could conquer the tubal dysfunction. In this case study, we report a PCD affected woman with infertility who was treated by IVF and pregnancy was achieved but it failed due to the spontaneous abortion. We also performed whole-exome sequencing for this case and her PCD-affected sister, which did not reveal any genetic abnormality related to the PCD or infertility.     

Effects of diode low-level laser therapy on healing of tooth extraction sockets: a histopathological study in diabetic rats

Lasers in Medical Science - Diabetes mellitus is mostly interrelated to deficiency in wound healing. Low-level laser therapy has been shown to exert reliable effects on the acceleration of wound...