β-Thalassemia Mutations in the Iranian Kurdish Population of Kurdistan and West Azerbaijan Provinces

The aim of this study was to investigate the prevalence and spectrum of β-thalassemia (β-thal) mutations in the population of Sunni Muslim Kurds in western Iran and to set up a prenatal diagnostic laboratory. Sixty unrelated Kurdish β-thal patients identified in hematology clinics from different cities were studied. The mutations in 120 chromosomes were studied by polymerase chain reaction–amplification refractory mutation system and direct sequencing methods. We found fifteen β-thal mutations, and IVS-II-1 (G>A) was the most frequent, comprising 35%?of all mutations. Other common mutations were frameshift codons 8/9 (+G) 15.7%, IVS-I-1 (G>A) 8%, FSC 5 (–CT) 6.7%, FSC 8 (–AA) 6.7%, and IVS-I-110 (G>A) 6%. This is the first comprehensive study in this region and could provide a reference for prenatal testing and genetic counseling in this population.     

Normal range determination of lymphocytes subsets in normal adults in Iran

Immunophenotyping of lymphocytes is very essential for evaluation of immune system. Due to the effect of environmental factors and ethical diversity on immune system, establishment of an internal normal range of lymphocyte subsets is a necessity for each population. The aim of this study was to determine the normal range of T and B lymphocytes, and NK cells in normal Iranian adults. Two hundred and thirty three Iranian normal adult volunteers took part in this study. Complete Blood Count (CBC) was performed for them with Sysmex (KX21) and cells with CD3, CD4, CD8, CD19 and CD16/56 surface markers were simultaneously detected by flow cytometry method with FACstar system. Their percentile and absolute count were determined.The volunteers were 150 male and 83 female. Mean percentages of lymphocyte subpopulation were: CD3 (67.66 ±7.76), CD19 (14.41±5.09), CD4 (39.22±6.7), CD8 (25.42 ±5.4) and CD16/56 (10.14±6.42). Also, their mean absolute count of lymphocyte bearing CD3, CD19, CD4 and CD8 were 1,504±505/μl, 332±186/μl, 827±313/μl and 522±185/μl, respectively.Our results are comparable with similar Asian results from other Asian population, but are different from European population, we therefore conclude that it is necessary for each laboratory to establish an internal normal range for the lymphocytes bearing above- mentioned markers.     

Takotsubo Cardiomyopathy (Acute Left Ventricular Apical Ballooning Syndrome) Occurring in the Intensive Care Unit

Objective Diagnosis of Takotsubo cardiomyopathy (also known as stress cardiomyopathy or acute left ventricular apical ballooning syndrome) can be challenging in patients who are being treated for other diseases in the intensive care unit, because symptoms could erroneously be attributed to the underlying disease or patients may not experience symptoms due to analgesia and sedation. The aim of our study was to assess clinical features of Takotsubo cardiomyopathy occurring in the intensive care unit.Design Prospective observational study.Setting University hospital.Patients Six consecutive patients diagnosed with Takotsubo cardiomyopathy who were being treated for other diseases in the intensive care unit.Interventions None.Measurements and main results Sudden hemodynamic deterioration (i.e., sudden hypotension, tachycardia or drop in monitored stroke volume) requiring vasopressor support was the presenting symptom in five of the six patients. Only one patient was able to report angina-like chest pain, all others were unable to experience symptoms due to analgesia and sedation. The electrocardiogram was abnormal in all patients upon diagnosis, demonstrating either ST-segment elevation (n = 2) and/or T-wave inversion (n = 5). Mild elevation of cardiac enzymes disproportionate to the extent of wall motion abnormalities on left ventriculography was present in all patients. All patients survived their acute event.Conclusions Sudden hemodynamic deterioration requiring vasopressor support and/or ECG abnormalities consisting of ST-segment elevation, ST-segment depression or T-wave inversion may be the presenting symptom of Takotsubo cardiomyopathy in the intensive care unit and should be included in the diagnostic algorithm.This work was carried out without any financial support. The authors have no financial interest in this article.     

Deposition, diffusion and transport mechanism of dry powder microparticulate salbutamol, at the respiratory epithelia

The deposition, dissolution and transport of salbutamol base (SB) and salbutamol sulfate (SS) inhalation powders were investigated using the Calu-3 air interface cell culture model and Franz diffusion cell. Drug uptake by cells was studied with respect to deposited dose, drug solubility and hydrophobicity. Furthermore, the role of active transport via organic cationic transporters (OCTs) was studied. SB and SS were processed to have similar diameters (3.09 ± 0.06 μm and 3.07 ± 0.03 μm, respectively) and were crystalline in nature. Analysis of drug wetting, dissolution and diffusion using a conventional in vitro Franz cell (incorporating a cell culture support Transwell polyester membrane) showed diffusion of SB to be slower than that of SS (98.57 ± 4.23 μg after 4 h for SB compared to 98.57 ± 4.01 μg after 15 min for SS). Such observations suggest dissolution to be the rate-limiting step. In comparison, the percentage transfer rate using the air interface Calu-3 cell model suggested SB transport to be significantly faster than SS transport (92.02 ± 4.47 μg of SB compared to 63.76 ± 8.84 μg of SS transported over 4 h), indicating that passive diffusion through the cell plays a role in transport. Furthermore, analysis of SB and SS transport, over a range of deposited doses, suggested the transport rate in the Franz diffusion cell to be limited by wetting of the particle and dissolution into the medium. However, for the cell monolayer, the cell membrane properties regulate the diffusion and transport rate. Analysis of the drug transport in the presence of triethylamine (TEA), a known inhibitor of OCTs, resulted in a significant decrease in drug transport, suggesting an active transport mechanism. The presence of OCTs in this cell line was further validated by Western blot analysis. Finally, the transport of SS from a commercial product (Ventolin Rotacaps) was studied and showed good agreement with the model SS system studied here.     

Monitoring of serum vancomycin concentrations in pediatric patients with normal renal function

Vancomycin is a a glycopeptide antibiotic with bacetiocidal effects on gram positive bacteria by interfering with cell wall synthesis. The necessity for monitoring of serum vancomycin concentrations (SVCs) has been recently noticed at many institutions because of concerns for its nephrotoxicity. We aimed to describe the SVCs monitoring in pediatric patients, in an effort to determine subtherapeutic or toxic levels. The medical records were reviewed for all patients older than 60 days of age admitted to the general or subspecialty services who received intravenous vancomycin at Children's Medical Hospital in Tehran, Iran between July 2003 and December 2005. Because pharmacokinetic parameters for children with cancer may be different, this group was evaluated separately. During the study, 167 infants and children without cancer and 42 patients with cancer; aged between 3 months to 17.5 years were treated with vancomycin for various infections. In children without cancer, peak SVCs were in an adequate therapeutic range for 93% of patients (8-55 microg/ml). For children with cancer, peak SVCs was lower than 10 microg/ml (10%), and trough values were lower than 5 microg/ml (21%). In conclusion, according to the results of this research, due to different pharmacokinetics of vancomycin in cancerous patients, the monitoring of vancomycin plasma concentrations is necessary for the best therapeutic antibacterial activities with a fewer occurrence of serious adverse effects.     

A Comprehensive Review on Pharmacotherapeutics of Three Phytochemicals,Curcumin, Quercetin,and Allicin,in the Treatment of Gastric Cancer

Objective

Gastric cancer is one of the most common causes of cancer-related death worldwide. Medicinal plants are one of the main sources for discovery of new pharmacological agents especially for treatment of cancers. The aim of the present study is to review pharmacotherapeutic aspects of three mostly studied phytochemicals including curcumin, quercetin, and allicin for management of gastric cancer.

Methods

Scopus, PubMed, Web of Science, and Google Scholar were searched for the effects of curcumin, quercetin, allicin, and their analogs in gastric cancer. Data were collected up to November 2015. The search terms were “curcumin,” “quercetin,” “allicin,” and “gastric cancer” or “cancer.”

Results

Curcumin demonstrated anti-angiogenic, anti-proliferative, anti-metastatic, pro-apoptotic, and anti-helicobacter activities. Quercetin inhibited cell growth and induced apoptosis, necrosis, and autophagy as well as anti-Helicobacter activity. Allicin showed apoptotic and anti-Helicobacter properties. All three natural compounds had low bioavailability.

Conclusions

Although preclinical studies demonstrated the activity of curcumin, quercetin, and allicin in gastric cancer, clinical trials are needed to confirm their effectiveness. Applying their possible synergistic action and suitable drug delivery system in clinical studies can be also an attractive approach with the purpose of finding new extremely efficient anti-gastric cancer agents.

Mini-Abstract

Curcumin, quercetin, and allicin seem to be good candidates for management of gastric cancer through their pro-apoptotic, anti-proliferative, and anti-helicobacter activities.

     

Plasminogen activator inhibitor-1 gene polymorphism in Iranian Azeri Turkish patients with FMF disease and its association with amyloidosis

Familial Mediterranean fever (FMF) is an autosomal recessive disorder characterized by intermittent episodes of fever with serositis, arthritis, or eriseplemya. Plasminogen activator inhibitor 1 (PAI-1) is a key element in the inhibition of fibrinolysis by inactivating tissue-type and urokinase-type plasminogen activators. We evaluated the association of PAI-1 -675 4G/5G polymorphism with the severity of FMF disease. For this purpose, 89 FMF patients with M694V homozygous mutation and 95 healthy controls from Iranian Azeri Turks were selected. Detection of this polymorphism was performed by polymerase chain reaction using allele-specific primers. No significant association was found between patients and control group. However, these data showed that FMF patients with M694V homozygous mutation carrying 4G/4G genotype have a reduced risk for development of pleuritis (odds ratios (OR) 0.36; 95 % confidence intervals (CI) 0.5–0.85; P value?=?0.007) compared with 5G/5G homozygotes who have increased risk for development of amyloidosis (OR?=?2.46; 95 %CI?=?1.29–4.72; P value?=?0.001), pleuritis (OR?=?2.55; 95 %CI?=?1.31–4.99; P value?=?0.001), and fever (OR?=?4.68; 95 %CI?=?2.04–10.96; P value?=?0.000). Furthermore, the allelic frequency of the 4G among the patients with pleuritis was significantly low (OR?=?0.5, 95 % CI?=?0.27–0.92, P value?=?0.008). Conclusion Our data suggest a protective role for the 4G allele against pleuritis in FMF patients with M694V homozygous mutation in this cohort. More evaluation of this polymorphism may be important and require further studies.     

Bilirubin/Albumin Ratio for Predicting Acute Bilirubin-induced Neurologic Dysfunction

Objective

The aim of this study was to evaluate the bilirubin albumin (B/A) ratio in comparison with total serum bilirubin (TSB) for predicting acute bilirubin-induced neurologic dysfunction (BIND).

Methods

Fifty two term and near term neonates requiring phototherapy and exchange transfusion for severe hyperbilirubinemia in Children''s Medical Center, Tehran, Iran, during September 2007 to September 2008, were evaluated. Serum albumin and bilirubin were measured at admission. All neonates were evaluated for acute BIND based on clinical findings.

Findings

Acute BIND developed in 5 (3.8%) neonates. B/A ratio in patients with BIND was significantly higher than in patients without BIND (P<0.001). Receiver operation characteristics (ROC) analysis identified a TSB cut off value of 25 mg/dL [area under the curve (AUC) 0.945] with a sensitivity of 100% and specificity of 85%. Also, according to the ROC curve, B/A ratio cut off value for predicting acute BIND was 8 (bil mg/al g) (AUC 0.957) with sensitivity of 100% and specificity of 94%.

Conclusion

Based on our results, we suggest using B/A ratio in conjunction with TSB. This can improve the specificity and prevent unnecessary invasive therapy such as exchange transfusion in icteric neonates.