Gout drugs use and risk of cancer: A case-control study

Objective

Firm conclusion about whether short and long-term gout medications use has an impact on cancer risk remain inconclusive. The aim of this study was to investigate the association between gout drugs use and risk of cancer.

Glutamine synthetase gene expression and glutamate transporters in C6-glioma cells

Glutamine synthetase (GS) is the major glutamate-forming enzyme of vertebrae and is accepted to be a marker of astroglial cells. Maturation of astroglial cells is characterized by an increase in GS activity, and the regulation of this enzyme is the topic of many publications. The amino acid glutamate is the major excitatory neurotransmitter in the brain and mediates normal excitatory synaptic transmission by interaction with postsynaptic receptors. Glutamate also acts as a potent neurotoxin when present at high concentration. Glutamate neurotoxicity plays an important role in the pathophysiology of many neurological disorders, such as Alzheimer’s disease, Huntington’s disease and amyotrophic lateral sclerosis. In the normal condition, L-glutamate is predominantly taken up, metabolized and recycled by astrocytes through the glutamate transporters (GLAST/GLT1) and glutamine synthetase (GS) catalytic activity. Because of the fundamental role of these glutamate transporters and the glutamine synthetase enzyme in controlling cerebral glutamate level, regulation of GS and studying of the glutamate transporters in glial cells is important. Astrocytes are supportive cells and act as the site of detoxification of glutamate in the brain. However, their isolation from the brain is a tedious, costly and time consuming procedure. On the other hand, the C6-glioma cells are readily available on the market. They are well characterized and have been a useful model for CNS glia in many laboratories. For this study, we used the C6-glioma cell line as a model system. We examined the presence or absence of glial specific glutamate transporters (GLTI and GLAST) in C6-glioma cells, which was done by immunocytochemistry. We also examined glutamine synthetase gene expression in these cells by treatment of the C6-glioma cells with estrogen (17ß estradiol). The findings from this study provide useful information about C6-glioma cells which makes the study of the CNS tremendously inexpensive.     

Correlation between E-cadherin and CD44 adhesion molecules expression and cervical lymph node metastasis in oral tongue SCC: Predictive significance or not

The aim of this article was to evaluate the expression of E-cadherin and CD44 adhesion molecule in oral tongue squamous cell carcinoma (SCC) since inappropriate expression of adhesion molecules raises the metastatic ability of the tumor cells.Biopsy specimens from 92 patients with tongue SCC were examined for the expression of E-cadherin and CD44 by immunohistochemistry. The relationship of immunoreactivity with tumor stage and cervical lymph node metastasis was then analyzed.Sixty-one patients (66.3%) had reduced or negative staining for CD44. Weak or absent staining for E-cadherin was seen in 14 patients (15.21%). Cervical lymph node metastasis is associated with decreased or negative staining for CD44, but no association was found between E-cadherin immunoreactivity and nodal metastasis.Our study reveals that reduced expression of CD44 could be an indicator of high invasiveness of tumor by increasing cervical lymph node metastasis.     

TP53 gene expression in HPV-positive oral tongue SCC and its correlation with nodal metastasis

In this study, we investigated the prevalence of human papilloma virus (HPV) infection and TP53 expression in patients with squamous cell carcinoma (SCC) of the tongue and, subsequently, its significance in cervical lymph node metastases and tumor differentiation. Sections of formalin-fixed, paraffin-embedded tissue blocks from 94 histologically confirmed tongue SCC cases were investigated in this study. Immunohistochemistry was used to study TP53 expression, and polymerase chain reaction (PCR) was performed for the detection of high risk HPV types (16 and 18). The frequency of HPV-16 and HPV-18 infection was 10.6% and 16%, respectively. Overexpression of TP53 was observed in 70.2% of patients. Young patients (aged below 45 years) comprised 20% of all patients. There was no significant association between TP53, HPV-16, or HPV 18 presence and higher stages of the tumor, tumor differentiation, or presence of nodal metastasis. Although an association between head and neck SCC and HPV infection is being recognized and reported, our data implicate that HPV infection or TP53 expression does not play a significant role in oral tongue SCC pathogenesis, differentiation, or metastasis, as seen in our patients.     

A large population-based study on the prevalence of electrocardiographic abnormalities: A result of Mashhad stroke and heart atherosclerotic disorder cohort study

Background

Twelve-lead electrocardiogram (ECG) is a common and inexpensive tool for the diagnostic workup of patients with suspected cardiovascular disease, both in clinical and epidemiological settings. The present study was designed to evaluate ECG abnormalities in Mashhad population.

Methods

ECGs were taken as part of MASHAD cohort study (phase1) and were coded according to the Minnesota coding criteria. Data were analyzed using SPSS.

Results

Total 9035 ECGs were available for final analysis including 3615 (40.0%) male and 5420 (60.0%) female. Among ECG abnormalities precordial Q wave, major T-wave abnormalities, inferior Q wave, sinus bradycardia, and left axis deviation were the most prevalent abnormalities. The frequency of precordial and inferior Q wave, inferior QS pattern, major and minor ST abnormalities, major and minor T abnormalities, Wolff-Parkinson-White and Brugada pattern, sinus bradycardia, sinus tachycardia, left axis deviation, ST elevation, and tall T wave were significantly different between two genders. Moreover, the frequency of Q wave in precordial and aVL leads, QS pattern in precordial and inferior leads, major and minor T-wave abnormalities, Wolff-Parkinson-White, atrial fibrillation, sinus bradycardia, left axis deviation, and ST elevation were significantly different in different age groups. A comparison of the heart rate, P-wave duration, and QRS duration between men and women indicated that there was a significant difference.

Conclusions

Our finding indicated that the prevalence ECG abnormalities are different between men and women and also it varied in different age groups.     

Endonasal microscopic removal of clival chordomas

INTRODUCTION: Clival chordomas have traditionally been removed using a variety of anterior and lateral skull base approaches. Herein, we evaluate the outcomes of patients who underwent an extended endonasal transsphenoidal removal of a clival chordoma. METHOD: All consecutive patients with a clival chordoma treated using an endonasal microscope approach were identified. In 8 cases, frameless surgical navigation was used, and in 4 cases, endoscopic assistance was used. Patients treated with prior radiotherapy were excluded. RESULT: Over 5 years, 18 procedures were performed on 14 patients (7 females; mean age, 47 years). Patients were followed from 3 to 58 months (median, 20 months). Mean tumor diameter was 32 +/- 17 mm; 7 (50%) patients had intradural extension. Postoperative MRIs after the initial operation showed gross total, near-total (>90%), and subtotal resection in 43%, 43%, and 14% of patients, respectively. Use of the endoscope was associated with gross total or near-total tumor removal in 4 of 4 cases. Tumor regrowth occurred in 2 (14%) cases 10 and 12 months after the initial surgery and before radiotherapy. Two patients had multiple operations, in one as a planned staged operation, and in the other, 3 additional debulkings were performed despite an initial gross total removal. Nine patients, all with CS invasion, had subsequent stereotactic radiation. Of 10 patients with cranial neuropathy, 80% improved or resolved including 75% and 67% of sixth and fifth CN palsies, respectively. Complications included one each of adrenal insufficiency and chemical meningitis. There were no CSF leaks or new neurological deficits. CONCLUSION: In this small series with relatively short follow-up, endonasal microscopic removal of clival chordomas proved safe and elfective with gross total or near-total removal in 86% of patients and improvement of cranial neuropathy in 80% of patients. Endoscopy for aiding tumor removal and assessing completeness of resection, as well as surgical navigation, are recommended for all cases.     

C2-linked alkynyl poly-ethylene glycol(PEG) adenosine conjugates as water-soluble adenosine receptor agonists

A series of 12 novel polyethylene-glycol(PEG)-alkynyl C2-adenosine(ADN) conjugates were synthesized using a robust Sonogashira coupling protocol and characterized by NMR spectroscopy and mass spectrometry analysis. The ADN-PEG conjugates showed null to moderate toxicity in murine macrophages and 12c was active against Mycobacterium aurum growth (MIC = 62.5 mg/L). The conjugates were not active against Mycobacterium bovis BCG. Conjugates 10b and 11b exhibited high water solubility with solubility values of 1.22 and 1.18 mg/ml, respectively, in phosphate buffer solutions at pH 6.8. Further, 10b and 11b induced a significant increase in cAMP accumulation in RAW264.7 cells comparable with that induced by adenosine. Analogues 10c , 11c and 12c were docked to the A₁, A_2A, A_2B and A₃ adenosine receptors (ARs) using crystal-structures and homology models. ADN-PEG-conjugates bearing chains with up to five ethyleneoxy units could be well accommodated within the binding sites of A₁, A_2A and A₃ ARs. Docking studies showed that compound 10b and 11b were the best A_2A receptor binders of the series, whereas 12c was the best binder for A₁ AR. In summary, introduction of hydrophilic PEG substituents at the C2 of adenine ring significantly improved water solubility and did not affect AR binding properties of the ADN-PEG conjugates.     

The study of H. pylori putative candidate factors for single- and multi-component vaccine development

Helicobacter pylori has grown to colonize inside the stomach of nearly half of the world’s population, turning into the most prevalent infections in the universe. Medical care failures noticeably confirm the need for a vaccine to hinder or deal with H. pylori. This review is planned to discuss the most known factors as a vaccine candidate, including single (AhpC, BG, CagA, KatA, Fla, Hsp, HWC, Lpp, LPS, NAP, OMP, OMV, SOD, Tpx, Urease, VacA) and multi-component vaccines. Many promising results in the field of single and multivalent vaccine can be seen, but there is no satisfactory outcome and neither a prophylactic nor a therapeutic vaccine to treat or eradicate the infection in human has been acquired. Hence, selecting suitable antigen is an important factor as an appropriate adjuvant. Taken all together, the development of efficient anti-H. pylori vaccines relies on the fully understanding of the interactions between H. pylori and its host immune system. Therefore, more work should be done on epitope mapping, analysis of molecular structure, and determination of the antigen determinant region as well due to design a vaccine, preferably a multi-component vaccine to elicit specific CD4 T-cell responses that are required for H. pylori vaccine efficacy.