Report on Patients with Non Transfusion-Dependent β-Thalassemia Major Being Treated with Hydroxyurea Attending the Thalassemia Research Center,Sari, Mazandaran Province,Islamic Republic of Iran in 2013

Hydroxyurea (HU) has been used to treat patients with non transfusion-dependent β-thalassemia major (β-TM) at the Thalassemia Research Center, Sari, Mazandaran Province, Islamic Republic of Iran since 1996. This study was performed to summarize and to share our experience. Medical records of all patients with β-thalassemia (β-thal) attending our center were reviewed in January 2013. Definition of β-TM was based on complete blood count (CBC), hemoglobin (Hb) electrophoresis, and for some patients, by the amplification refractory mutation system-restriction fragment length polymorphism (ARMS-RFLP) method. Patients who had not been transfused before, or had only occasionally had blood transfusions, were selected. Age at first blood transfusion, initial HU therapy and time of study was extracted from the records. The lowest Hb level before using HU and the last Hb value when on the HU regimen as well as the difference, were reported. Number of saved packed red cells was calculated according to duration of HU use and the usual needs of the patients. Hydroxyurea was discontinued before a planned pregnancy and during gestation and lactation periods. Hydroxyurea was discontinued for male patients willing to reproduce. A p value of <0.05 was considered statistically significant. It was consistent with 1856 patients/year, and 3542 units of blood were saved. We found HU to be effective and safe in treating patients with non transfusion-dependent β-TM. We strongly recommend HU therapy.     

Role of nitric oxide in the rat hippocampal CA1 area on morphine-induced conditioned place preference

Effects of intrahippocampal CA1 injections of L-arginine, a nitric oxide (NO) precursor, and N(G)-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor, on morphine-induced conditioned place preference in male Wistar rats were investigated. Animals received subcutaneous (s.c.) injections of saline (1.0 ml/kg) or morphine (0.5-7.5 mg/kg) once daily for 3 days to induce conditioned place preference. The administration of L-arginine (0.3, 1.0, and 3.0 microg/rat), but not L-NAME (0.3, 1.0, and 3.0, microg/rat), prior to administration of morphine (5.0 mg/kg) during acquisition of morphine-induced conditioned place preference increased morphine-induced conditioned place preference, but the interaction between the response to morphine and/or L-arginine was not statistically significant. The response to L-arginine was blocked by L-NAME pre-administration. L-Arginine or L-NAME by itself did not induce conditioned place preference. The administration of L-arginine but not L-NAME, 1 min before conditioned place preference testing, increased the expression of morphine-induced conditioned place preference. Pre-administration of L-NAME blocked the L-arginine response. It is concluded that NO in the rat hippocampal CA1 area may be involved in morphine-induced conditioned place preference.     

Influence of nitric oxide on morphine-induced conditioned place preference in the rat central amygdala

Effects of intra-central amygdala injections of L-arginine, a nitric oxide (NO) precursor, and N(G)-nitro-L-arginine methyl ester (L-NAME), a NO synthase (NOS) inhibitor, on morphine-induced conditioned place preference in rats were investigated by using an unbiased 3-day schedule of place conditioning design. Animals receiving once daily injections of morphine (0.5-7.5 mg/kg, subcutaneously, s.c.) or saline (1.0 ml/kg, s.c.) showed a significant place preference in a dose-dependent manner. The maximum response was observed with 5.0 mg/kg of the opioid. Co-administration of morphine (5.0 mg/kg) with L-arginine (0.3, 1.0 and 3.0 microg/rat), but not with L-NAME (0.3, 1.0 and 3.0 microg/rat), during the acquisition of morphine-induced conditioned place preference increased morphine-induced conditioned place preference. The response to L-arginine was blocked by L-NAME preadministration. L-arginine and L-NAME by themselves did not induce conditioned place preference. When L-arginine or L-NAME at 0.3-3.0 microg/rat was administered 1 min before conditioned place preference testing, L-arginine but not L-NAME caused an increase in the expression of morphine-induced conditioned place preference, the effect that was blocked by L-NAME preadministration. A dose of L-arginine (0.3 microg/rat), but not L-NAME, during expression of morphine-induced conditioned place preference produced an increase in locomotion compared with that in the control group. It may be concluded that an increase in the NO levels in the central amygdala may have an effect on the acquisition and expression of morphine-induced conditioned place preference.     

Sulpiride injections into the medial septum reverse the influence of intra-medial septum injection of L-arginine on expression of place conditioning-induced by morphine in rats

Effects of intra-medial septum injections of L-arginine, a precursor of nitric oxide, N(G)-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase, and sulpiride, a selective antagonist of dopamine D2 receptor on morphine-induced conditioned place preference (CPP) in male Wistar rats were examined. Using a 3-day schedule of conditioning, morphine (0.5-7.5 mg/kg, s.c.) produced a significant place preference in a dose-dependent manner. The maximum response was observed with 5.0 mg/kg of opioid. Sulpiride (0.3, 1.0 and 3.0 microg/rat), but not L-arginine (0.3, 1.0 and 3.0 microg/rat) or L-NAME (0.3, 1.0 and 3.0 microg/rat), in combination with morphine (5.0 mg/kg), during conditioning, significantly altered morphine-induced CPP. Single doses (0.3, 1.0 and 3.0 microg/rat) of either L-arginine or L-NAME, during conditioning, did not induce CPP. Sulpiride at 0.3-3.0 microg/rat, intra-medial septum, during conditioning, produced a significant conditioned place aversion. Intra-medial septum injections of L-arginine but not L-NAME or sulpiride, 1-2 min before testing, increased the expression of morphine-induced CPP. The administration of sulpiride (0.3, 1.0 and 3.0 microg/rat), but not L-NAME (0.3, 1.0 and 3.0 microg/rat), 1-2 min before the injection of L-arginine (0.3 microg/rat) on day of test, significantly attenuated the response to L-arginine. L-Arginine (0.3-3.0 microg/rat), during conditioning, showed a statistically significant increase in locomotor activity compared with that to control group. Moreover, sulpiride decreased locomotion by itself or in combination with morphine during conditioning and on the test day of morphine CPP. It can be concluded that L-arginine, a precursor of nitric oxide, in the rat median septum may play a role in expression of morphine conditioning due to dopamine release in this area.     

Totally tubeless percutaneous nephrolithotomy in selected patients

PURPOSE: Significant early postoperative discomfort after percutaneous procedures is usually secondary to nephrostomy tubes and externalized ureteral catheters. We describe our modification of the traditional percutaneous nephrolithotomy (PCNL) approach that we name "totally tubeless PCNL." PATIENTS AND METHODS: Between June 2000 and May 2001, 60 consecutive PCNLs were performed at our centers. At the end of the surgery, we omitted the nephrostomy tube and removed the externalized catheter in selected patients: no solitary kidney, stone size <3 cm, and without any obstructions or arterial bleeding. A total of 30 patients underwent totally tubeless PCNL (group 1). We compared their results with those of a control group of 30 patients who underwent standard PCNL (group 2). The incidence of complications, analgesic requirements, length of hospitalization, and time to return to normal activities were compared in the two groups. RESULTS: In both groups, PCNL was performed successfully without any significant complications. A 90% stone-free rate was achieved in both groups, and in the remaining patients, small residual stones (<4 mm) were detected. No urinoma was demonstrated by postoperative ultrasound scanning in group 1. The average length of hospitalization was 1.5 days for group 1 and 3 days for group 2. The average analgesic requirements were 30 mg of pentazosin in group 1 and 90 mg in group 2. No transfusion was needed. There were three complications: 2 patients (6.6%) had urinary tract infection in group 1 and 1 (3.3%) in group 2. All were managed medically. CONCLUSIONS: Omitting the percutaneous nephrostomy tube and removing ureteral catheter at the end of surgery in selected patients were safe and accompanied by significantly reduced postoperative discomfort, length of hospitalization, and analgesic requirements. Further studies are needed to determine the role of this technique.     

Production of monoclonal antibody,PR81, recognizing the tandem repeat region of MUC1 mucin

A monoclonal antibody (MAb) was generated by immunizing BALB/c mice with homogenized breast cancerous tissues. This antibody (PR81) was found to be of IgG(1) class and subclass, containing kappa light chain. PR81 reacted with either the membrane extracts of several breast cancerous tissues or the cell surface of some MUC1 positive cell lines (MCF-7, BT-20 and T-47D) tested by enzyme immunoassay and for MCF-7 by immunofluorescence method. PR81 also reacted with two synthetic 27 and 16-amino acid peptides, TSA-P1-24 and A-P1-15, respectively, which included the core tandem repeat sequence of MUC1. However, this antibody did not react with a synthetic 14 amino acid peptide that has no similarity with tandem repeat found in MUC1. The generated antibody had good and similar affinities (2.19 x 10(8) M(-1)) toward TSA-P1-24 and A-P1-15, which are mainly shared in the hydrophilic sequence of PDTRPAP. Through Western blot analysis of homogenized breast tissues, PR81 recognized only a major band of 250 kDa. This band is stronger in malignant tissue than benign and normal tissues.     

黄豆提取物的雌激素依赖作用对戊四唑诱发的大鼠癫痫的影响

目的：研究黄豆提取物对经戊四唑（pentylenetrazole,PTZ）诱发癫病发作的女性荷尔蒙缺失雌性大鼠与正常雌性大鼠的不同作用,以及因性别差异引起的植物雌性激素对行为的影响。方法：雄性Wistar大鼠被随机分为雄性生理盐水组,雄性低、中、高剂量黄豆提取物治疗组,每组8只;雌性Wistar大鼠随机分为假手术生理盐水组,假手术低、中、高剂量黄豆提取物治疗组,去卵巢生理盐水组,去卵巢低、中、高剂量黄豆提取物治疗组,每组8只。去卵巢大鼠在氯胺酮麻醉下行卵巢切除术。分别给予各组大鼠生理盐水及不同剂量黄豆提取物治疗2周后腹腔内注射戊四唑。将大鼠放置在树脂玻璃笼内,记录最小阵挛性癫痫发作（minialclonicseizure,MCS）潜伏期和强直性阵挛性癫痫发作（generalizedtonic-clonicseizure,GTCS）潜伏期。结果：与雄性生理盐水组大鼠比较,雄性低、中剂量黄豆提取物治疗组的MSC和GTCS潜伏期显著缩短（P〈10．05或P〈0．01）。雌性假手术大鼠在给予黄豆提取物治疗后,其MSC和GTCS潜伏期没有显著改变。与去卵巢生理盐水组比较,去卵巢低、高剂量黄豆提取物治疗组的MSC和GTCS潜伏期明显缩短（P〈0．05或P〈0．01）。结论：黄豆的植物雌激素能影响由PTZ诱发的癫痫发作的轻重程度,但其影响程度与卵巢激素水平有关。机制还有待进一步研究。     

Video-assisted thoracoscopic surgery (VATS) for the treatment of scolioticrib hump deformity

A retrospective study of 21 patients with idiopathic scoliosis who underwent endoscopic thoracoplasty was done. The objective of the study was to report and assess the morbidity and mid term outcomes of video-assisted thoracoplasty in idiopathic scoliosis. Patients with idiopathic scoliosis often present cosmetic complaints due to their rib deformity. This deformity may still exist after surgical correction of the main scoliotic curve. Endoscopic thoracoplasty has been reported as a safe method in limited cases of idiopathic scoliosis. Between 2002 and 2004, 21 patients underwent endoscopic anterior release and thoracoplasty for significant rib hump deformity associated with idiopathic scoliosis. Patients were operated on lateral position, with two endoscopic ports. Anterior release and rib resection were performed during the first stage, and instrumented posterior fusion was performed in a second stage. Patients were evaluated preoperatively, 1 week after surgery, 6 months after surgery and at their most recent follow-up with clinical and radiological measurement of the rib deformity. The mean age at surgery was 14.9 years old (range 13–17 years). The average Cobb’s angle of the main scoliotic curve was 70° (range 60°–85°). Average follow-up was 25 months (range 23–32 months). The mean number of resected ribs was five ribs (range 4–7) and the mean length of the resected rib was 4.2 cm (range 2.2–7 cm). Average operating time of endoscopic thoracoplasty (including anterior release) was 65 min (range 45–108 min). The mean preoperative height of rib hump deformity was 3.6 cm (range 2.5–5.5 cm). It was reduced to 1.5 cm at most recent follow-up. There was no significant thoracic pain necessitating medication postoperatively. No complications related to endoscopic anterior release and rib hump resection occurred in the series. Endoscopic thoracoplasty is a safe and reliable technique in idiopathic scoliosis. If indicated, the anterior release can be performed with video-assistance and the thoracoplasty can be performed on the same stage.     

Epigenetic involvement in etiopathogenesis and implications in treatment of systemic lupus erythematous

Background

Recent researches in the field of genetics have extended our knowledge through the discovery of genetic factors associated with autoimmune diseases (AID). Genetics by itself, however, cannot elucidate all the uncertainties encountered in the etiopathology of AID. On the other hand, incomplete harmony in the prevalence of AID in identical twins suggests that non-genetic factors may play an important role in determining the disease susceptibility. Besides, epigenetics, which is defined by changes in gene expression without a corresponding change in the DNA sequences, has come in to provide new awareness in the disease etiopathology by bridging the genetic and epigenetic factors. The recent advances in the field of epigenetics provide a new insight into the understanding of the disease mechanisms, development, diagnostic and prognostic approaches, as well as the various treatment methods.

Purpose

This review paper aims to present an overview of epigenetic modifications involved in the pathogenesis of systemic lupus erythematosus (SLE) and discuss their important roles in clinical and pharmacological settings, including novel and recent therapeutic applications.

Results

Nowadays, it is believed that autoimmune diseases, such as SLE, begin when genetically susceptible factors associate with environmental triggers. The current therapeutic approaches for SLE treatment have been based on treatments with immunosuppressive drugs, which are linked to various side effects. It is difficult to develop highly effective treatments for SLE patients with minimal or no side effects, mainly due to the disease complexity. The breakthrough of pharmacoepigenetics provides a new approach to solve this problem. Epigenetic modifications can influence the efficacy of drugs by changing the gene expression through modifying chromatin remodeling. In this regard, epigenetic studies in SLE are expected to reveal novel disease biomarkers and therapeutic targets.

Conclusions

Accumulating evidence disclosed that epigenetic dysregulations are engaged in SLE pathogenesis and may be exerted as biomarkers to diagnose and as tools to treat these patients.

     

Angioedema Related to Angiotensin-Converting Enzyme Inhibitors: Attack Severity,Treatment, and Hospital Admission in a Prospective Multicenter Study

The number of cases of acquired angioedema related to angiotensin converting enzyme inhibitors induced (ACEI-AAE) is on the increase, with a potential concomitant increase in life-threatening attacks of laryngeal edema. Our objective was to determine the main characteristics of ACEI-AAE attacks and, in doing so, the factors associated with likelihood of hospital admission from the emergency department (ED) after a visit for an attack.A prospective, multicenter, observational study (April 2012–December 2014) was conducted in EDs of 4 French hospitals in collaboration with emergency services (SAMU 93) and a reference center for bradykinin-mediated angioedema. For each patient presenting with an attack, emergency physicians collected demographic and clinical presentation data, treatments, and clinical course. They recorded time intervals from symptom onset to ED arrival and to treatment decision, from ED arrival to specific treatment with plasma-derived C1-inhibitor (C1-INH) or icatibant, and from specific treatment to onset of symptom relief. Attacks requiring hospital admission were compared with those not requiring admission.Sixty-two eligible patients with ACEI-AAE (56% men, median age 63 years) were included. Symptom relief occurred significantly earlier in patients receiving specific treatment than in untreated patients (0.5 [0.5–1.0] versus 3.9 [2.5–7.0] hours; P < 0.0001). Even though icatibant was injected more promptly than plasma-derived C1-INH, there, however, was no significant difference in median time to onset of symptom relief between the 2 drugs (0.5 [0.5–1.3] versus 0.5 [0.4–1.0] hours for C1-INH and icatibant, respectively, P = 0.49). Of the 62 patients, 27 (44%) were admitted to hospital from the ED. In multivariate analysis, laryngeal involvement and progressive swelling at ED arrival were independently associated with admission (Odds ratio [95% confidence interval] = 6.2 [1.3–28.2] and 5.9 [1.3–26.5], respectively). A favorable course was observed in all patients. Three patients (5%) experienced a recurrence after angiotensin-converting enzyme inhibitor discontinuation after a median follow-up of 18 (11–30) months.Two severity criteria—laryngeal edema and the progression of the edema—were independent factors associated with likelihood of hospital admission. Appropriate specific treatments (plasma-derived C1-INH or icatibant) should be available in EDs to prevent possibly life-threatening complications.