Evidence for the role of nitric oxide in nicotine-induced locomotor sensitization in mice

Rationale Nitric oxide (NO) is implicated in both acute effects of addictive drugs and development of dependence to them. We investigated the role of NO in nicotine-induced locomotor sensitization.Objectives The effects of N-nitro-l-arginine methyl ester (l-NAME), a NO synthase inhibitor, and a combination of a NO precursor l-arginine and l-NAME on nicotine-induced locomotor sensitization were investigated in Swiss Webster mice.Methods Sensitization to psychomotor stimulating effect of nicotine was rendered by seven injections of nicotine (1 mg/kg) on every other day. To investigate their effect on the development of sensitization to nicotine, l-NAME (15–60 mg/kg) and l-arginine (1 g/kg) were given before nicotine administration during the first seven sessions. To investigate the effect of these compounds on the expression of nicotine sensitization, after a 4-day drug-free period another group of mice received a challenge injection of nicotine on day 18.Results Nicotine (1 mg/kg) produced a robust locomotor sensitization in mice. The doses of 30 mg/kg and 60 mg/kg of l-NAME blocked the development of sensitization to nicotine; and, l-arginine (1 g/kg) pretreatment reversed this effect of l-NAME. Likewise, the doses of 30 mg/kg and 60 mg/kg of l-NAME inhibited the expression of sensitization to nicotine on day 18; and, l-arginine (1 g/kg) pretreatment reversed this inhibitory effect of l-NAME.Conclusions Our results suggest that NO is implicated in the development and expression of nicotine-induced locomotor sensitization in mice.     

Association of tumour necrosis factor-alpha -308 G/A polymorphism with primary open-angle glaucoma

Background: Tumour necrosis factor‐alpha (TNF‐α) is an important proinflammatory cytokine driving axonal degeneration and retinal ganglion cell apoptosis in glaucoma. The aim of the study was to evaluate the association of TNF‐α ‐308 G/A and ‐238 G/A polymorphisms with primary open‐angle glaucoma (POAG). Design: A prospective, case–control study, university hospital setting. Participants: Eighty‐six POAG patients and 193 healthy unrelated controls. Methods: TNF‐α polymorphisms were screened by using direct gene sequencing. Main Outcome Measures: Frequency of TNF‐α ‐308 G/A and TNF‐α ‐238 G/A promoter polymorphisms in glaucoma and healthy subjects. Results: The frequencies of TNF‐α ‐308 GA genotype and ‘A’ allele were higher in patients with POAG (22.1% and 12.2%, respectively) in comparison with the control group (10.9% and 6%, respectively) (P = 0.046 and 0.02, respectively), with odds ratios of 2.45 (P = 0.01, 95% CI = 1.23–4.87) and 2.19 (P = 0.013, 95% CI = 1.18–4.08), respectively. Genotype distribution of the TNF‐α ‐238 variants did not yield a statistically significant difference between the two groups (P = 0.87). Conclusion: TNF‐α ‐308 G/A polymorphism seems to be associated with POAG in Turkish population. However, population‐based studies with large number of subjects and long‐term follow‐up are needed to verify the association of TNF‐α ‐308 G/A polymorphism with glaucoma susceptibility.     

PRAME mRNA levels in cases with acute leukemia: clinical importance and future prospects

The PRAME (preferentially expressed antigen of melanoma) gene has been shown to be expressed in high levels in some solid tumors and hemopoietic neoplasias but not or only weakly expressed in normal tissues. It encodes an antigen recognized by autologous cytolytic T lymphocytes. PRAME is a good candidate for tumor immunotherapy and is a useful marker gene for detection of minimal residual disease (MRD). In this study, PRAME mRNA using real-time RT-PCR was studied in 74 adult cases with acute leukemia-68 had de-novo acute leukemia, 3 had chronic myeloid leukemia-blastic crisis (CML-BC), and 3 had myelodysplastic/myeloproliferative syndrome-blastic transformation (MDS/MPD-BT)-and the results were compared with 30 age-matched healthy volunteers. Nineteen of 74 cases with leukemia expressed PRAME, while only 2 controls showed weak expression. The prevalence of PRAME expression in AML and ALL cases was 30% and 17%, respectively. We did not find any important correlation between PRAME expression and clinical characteristics, such as age, sex, organomegaly/lymphadenopathy, Hb, WBC count, platelet count, LDH level, alkaline phosphatase, albumin, cell-surface antigens, response to therapy, or progression-free and overall survival. PRAME was monitored in 15 cases during remission and/or relapse. There was a good correlation between PRAME mRNA and hematological remission and/or relapse. Interestingly, PRAME was very high in one case with AML but was not found 3 months after allogeneic transplantation. PRAME mRNA is observed in about one-third of AML cases; it may be a useful marker to detect MRD, and it may also be a good predictor for the timing of donor lymphocyte infusions (DLI) in the post-transplant period in cases of molecular relapse.     

An infrequent cause of upper gastrointestinal tract bleeding: "Dieulafoy's lesion"

BACKGROUND/AIMS: Dieulafoy's lesions are uncommon sources of upper gastrointestinal tract bleeding. Endoscopists must be aware of these lesions when evaluating patients with upper gastrointestinal tract bleeding. METHODOLOGY: The aim of this study is to analyze the results of active bleeding or recurrently bleeding Dieulafoy's lesions treated either by endoscopic injection therapy (EIT) or endoscopic band ligation (EBL). Fifteen patients who had active bleeding due to Dieulafoy's lesions were evaluated retrospectively with respect to demographic properties, comorbidities, endoscopic therapy procedures, and the success rate of the procedure. RESULTS: The incidence of Dieulafoy's lesions was 4.5% in all cases of upper gastrointestinal tract bleeding. Among the 15 patients there were nine men and six women with a median age of 52 years (25-84 years). Eleven of these lesions were located in the stomach, two were in the duodenum, and two were in the distal esophagus. Eight patients were initially treated by EIT and seven patients had EBL therapy. There was no recurrent bleeding in any of the patients treated with EBL, but five patients (62.5%) treated with EIT bled again and were treated secondarily with EBL. Two of these patients required surgical intervention and one died on the 15th day of surgery due to myocardial infarction. No endoscopy-related complications were detected. CONCLUSIONS: Endoscopic methods should be the first choice in treating bleeding Dieulafoy's lesions. Both EIT and EBL are successful methods for achieving initial hemostasis. However, EIT therapy has a higher re-bleeding rate. EBL is a safe and effective method for the treatment of bleeding Dieulafoy's lesions.     

Pneumocystis carinii pneumonia in a rheumatoid arthritis patient treated with adalimumab

Patients with rheumatoid arthritis (RA) have an increased risk of infection as a result of alterations in immune regulation, debility, and comorbid illnesses. TNF-alpha is of central importance in the pathophysiological responses to infection and inflammation, and plays a crucial role in host defence. Pneumocystis carinii is an opportunistic pathogen that commonly affects individuals with inadequate T-cell mediated immune response. Patients with acquired immune deficiency, as well as those receiving immunosuppressive drugs for various conditions have an increased risk of P. carinii pneumonia (PCP). We report the development of PCP in a woman with RA shortly after the initiation of anti-TNF-alpha treatment with adalimumab.     

Tuberculosis of the knee joint: a case report

Tuberculosis may develop in the skeletal system apart from its primary location, the lungs. A 22-year-old male patient presented with complaints of severe pain and swelling in the left knee and difficulty in walking. The symptoms first appeared 12 years before and he underwent open surgical debridement and arthroscopic debridement at two other centers, at which time aspiration cultures taken from the knee yielded no growth. Physical examination showed a painful left knee with swelling, increased temperature, effusion, and limited range of motion. Based on history, physical examination, radiological studies, and laboratory findings, knee osteoarthritis was considered secondary to nonspecific septic arthritis and knee arthrodesis was performed. At surgery, marked destruction of articular cartilage and synovial hypertrophy were observed. In addition, a cavitary lesion was detected, about 1 x 1 cm in size, in the lateral femoral condyle without articular involvement. Biopsy cultures taken from the lesion showed growth of Mycobacterium tuberculosis in the third week. This enabled a diagnosis of tuberculosis of the knee joint and antituberculous drug therapy was instituted. At six months postoperatively, the patient was on antituberculous treatment and had a painless knee.     

Gastric volvulus after laparoscopic left adrenalectomy: case report

In this era of modern technologies, laparoscopic adrenalectomy is a gold standard surgical treatment for benign adrenal lesions. However, being aware of its difficulties and their managements is a very important issue for the surgeons who are interested in minimal invasive surgery. In this article, we are presenting a case of a 57-year-old woman who has undergone laparoscopic left adrenalectomy and in the third postoperative month, had an acute gastric volvulus requiring surgical open treatment. To the best of our knowledge, this report is the first article about a gastric volvulus case after left laparoscopic adrenalectomy.     

Amphotericin B deoxycholate (d-AMB) use in cases with febrile neutropenia and fungal infections: lower toxicity with suitable premedication

In spite of the development of new antifungal drugs, amphotericin B deoxycholate (d-AMB) remains the gold standard in the treatment of severe fungal infections in immunosuppressed hosts. However, d-AMB is a toxic drug, the most important dose-limiting toxicities being nephrotoxicity and infusion-related allergic reactions. Lipid and liposomal formulations of d-AMB have relatively lower toxicity and are considered alternative choices. However, the routine use of these formulations is limited by their higher cost. Using retrospective analysis, we explored the incidence of nephrotoxicity and allergic reactions requiring the cessation of conventional d-AMB in 113 cases treated with the drug. In contrast to knowledge in the relevant literature, we did not detect significant toxicity, which would have required discontinuation of the d-AMB treatment. Mean serum creatinine levels were 0.72 +/- 0.25 and 0.84 +/- 0.31 mg dl(-1) before and after therapy, respectively. Although the difference between creatinine levels before and after d-AMB is statistically significant, the creatinine level increased twofold in only eight cases. Mean serum potassium levels were 3.8 +/- 0.54 and 3.6 +/- 0.7 mmol l(-1) before and after d-AMB respectively. Potassium levels below 3 mmol l(-1) were found in 7 and 17 cases before and after d-AMB respectively. Potassium levels were statistically lower in cases with fungal mucositis. Severe infusion-related allergic reactions were observed in three cases. Antihistamine and corticosteroid were added to the treatment in these cases. With these findings, we can conclude that d-AMB is a tolerable, low cost drug which can be safely used provided there is suitable premedication and monitoring of blood urea nitrogen, serum potassium and magnesium levels.