Certain haplotypes of the 3'-UTR region of the HLA-G gene are linked to breast cancer.

Background: Human leukocyte antigen G belongs to the family of non-classical HLA class I genes, its expression considered an important immune escape mechanism of cancer cells. The polymorphisms in the 3'-untranslated region (UTR) region of HLA-G influence the magnitude of the protein by modulating HLA-G mRNA stability. We hypothesised links between any of eight (UTR) single nucleotide polymorphisms (SNPs) and their haplotype of the HLA-G gene with breast cancer. Materials and Methods: Peripheral blood DNA from 100 patients affected by breast cancer and 100 controls was PCR sequenced for genotyping of 25 HLA-G 3'-UTR regions, including rs371194629 (+2960), rs1707 (+3003), rs1710 (+3010), rs17179101 (+3027), rs1063320 (+3142), rs9380142 (+3187), rs1610696 (+3196), and rs1233331 (+3227). Results: The 14-bp deletion (p = 0.01), and the +3010 (p = 0.021), +3142 (p = 0.006) and +3187 (p = 0.046) variants were significantly more prevalent in patients than in controls. In combining these data, two haplotypes of all eight SNPs and deletion/insertion (UTR-1 and UTR-4) are associated with breast cancer. Conclusion: Certain variants in the 3-UTR, and their combination as a haplotype, of the HLA-G gene are linked to breast cancer.

Lupus hepatitis, more than just elevated liver enzymes.

Systemic lupus erythematosus (SLE), a multisystem autoimmune inflammatory disease, may involve any organs, including the liver. Liver involvement in SLE is not part of the American College of Rheumatology criteria and is relatively rare. Liver disease is usually mild, manifesting as subtle elevation of liver enzymes. Jaundice and hepatomegaly can be seen in some patients; advanced liver disease with cirrhosis is extremely rare. Precise pathology remains obscure. SLE may cause non-specific changes, including hepatocellular, cholestatic, or vascular changes. Alcohol, drugs, viral infections, metabolic disorders, autoimmune hepatitis, and other common causes of liver dysfunction should be excluded. Corticosteroids may expedite the recovery process, but may lead to non-alcoholic fatty liver disease and liver damage. Several large-scale multicentre studies have shown that liver involvement is not the major cause of morbidity and mortality in SLE patients. In this review, we discuss the pathogenesis, diagnosis, differential diagnosis, clinical manifestations, management, complications, and prognosis of lupus hepatitis.

On lithium doping in two stable nano-flakes of the B24: The double-ring versus the quasiplanar configuration.

The stable local minima due to the addition of the Li atom to the double-ring and the quasiplanar configurations of the B24 molecule have been searched on the doublet potential energy surface to reveal the structural and electronic features of the Li@B24 system. We report two and seven stable local minima without imaginary vibrational frequency for the Li@B24(double-ring) and the Li@B24(quasiplanar) systems, respectively. The criteria of the adsorption energy, the vertical ionization (VI) energy, the deformation energy, the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) energy gap, the atomic charges, the spin density distribution, the electron transfer (ET), atoms in molecules (AIM) analysis and the nonlinear optical (NLO) properties have been investigated for all the reported molecules of the Li@B24 system in the present paper. Our results present that both thermodynamic and chemical stability of the Li atom doping to the quasiplanar configuration of the B24 molecule are more than those of the double-ring configuration. Additionally, both the double-ring and the quasiplanar configurations can produce the Li@B24 system with values of high first hyperpolarizability (ßtotal) due to the Li atom doping. In all the reported molecules of the Li@B24 system, electron density of the Li atom decreases due to the existence of the double-ring and the quasiplanar configurations confirming the role of the electron donor for the Li atom. In contrast, both decreasing and increasing electron density have been observed in the B atoms of the Li@B24 system. However, the role of electron acceptor (increasing electron density) for the B atoms is more dominant than the role of electron donor (decreasing electron density). This result highlights chemical flexibility of the B atoms.

Protective effects of Cornus mas fruit extract on carbon tetrachloride induced nephrotoxicity in rats.

Oxidative damage is implicated in the pathogenesis of kidney injury. Cornus mas is used for in renal aliments traditionally in Iran. The present study was aimed to investigate the antioxidant activity of C. mas fruit extract (CMFE) on carbon tetrachloride (CCl4) treated oxidative stress in Wistar albino rats. Forty two male albino rats were divided into seven groups. Group I served as a sham; Group II served as a normal control; Group III served as a toxic control, with CCl4 (1 ml/kg body weight; 80% in olive oil); Groups IV and V received CMFE at doses of 300 and 700 mg/kg before CCl4 injection; Groups VI and VII received extract at same doses orally at 2, 6, 12, 24 and 48 h after CCl4 intoxication. CCl4 injection produced a significant rise in serum markers of oxidative stress and lipid peroxidation product malondialdehyde along with the reduction of antioxidant enzymes such as superoxide dismuta, catalase and glutathion peroxidase. Serum creatinine, urea and uric acid concentrations were increased whereas level of protein and albumin were reduced. Treatment of rats with different doses of fruit extract (300 and 700 mg/kg) significantly (P < 0.05) ameliorated the alterations induced with CCl4 in lipid peroxidation, antioxidant defenses, biochemical and renal lesions. Based on these results, we conclude that CMFE protects kidney from oxidative stress induced by CCl4.

Towards the bioequivalence of pressurised metered dose inhalers 1: design and characterisation of aerodynamically equivalent beclomethasone dipropionate inhalers with and without glycerol as a non-volatile excipient.

A series of semi-empirical equations were utilised to design two solution based pressurised metered dose inhaler (pMDI) formulations, with equivalent aerosol performance but different physicochemical properties. Both inhaler formulations contained the drug, beclomethasone dipropionate (BDP), a volatile mixture of ethanol co-solvent and propellant (hydrofluoroalkane-HFA). However, one formulation was designed such that the emitted aerosol particles contained BDP and glycerol, a common inhalation particle modifying excipient, in a 1:1 mass ratio. By modifying the formulation parameters, including actuator orifice, HFA and metering volumes, it was possible to produce two formulations (glycerol-free and glycerol-containing) which had identical mass median aerodynamic diameters (2.4µm±0.1 and 2.5µm±0.2), fine particle dose (⩽5µm; 66µg±6 and 68µg±2) and fine particle fractions (28%±2% and 30%±1%), respectively. These observations demonstrate that it is possible to engineer formulations that generate aerosol particles with very different compositions to have similar emitted dose and in vitro deposition profiles, thus making them equivalent in terms of aerosol performance. Analysis of the physicochemical properties of each formulation identified significant differences in terms of morphology, thermal properties and drug dissolution of emitted particles. The particles produced from both formulations were amorphous; however, the formulation containing glycerol generated particles with a porous structure, while the glycerol-free formulation generated particles with a primarily spherical morphology. Furthermore, the glycerol-containing particles had a significantly lower dissolution rate (7.8%±2.1%, over 180min) compared to the glycerol-free particles (58.0%±2.9%, over 60min) when measured using a Franz diffusion cell. It is hypothesised that the presence of glycerol in the emitted aerosol particles altered solubility and drug transport, which may have implications for BDP pharmacokinetics after deposition in the respiratory tract.

Towards the bioequivalence of pressurised metered dose inhalers 2. Aerodynamically equivalent particles (with and without glycerol) exhibit different biopharmaceutical profiles in vitro.

Two solution-based pressurised metered dose inhaler (pMDI) formulations were prepared such that they delivered aerosols with identical mass median aerodynamic diameters, but contained either beclomethasone dipropionate (BDP) alone (glycerol-free formulation) or BDP and glycerol in a 1:1 mass ratio (glycerol-containing formulation). The two formulations were deposited onto Calu-3 respiratory epithelial cell layers cultured at an air interface. Equivalent drug mass (∼1000ng or ∼2000ng of the formulation) or equivalent particle number (1000ng of BDP in the glycerol-containing versus 2000ng of BDP in the glycerol-free formulation) were deposited as aerosolised particles on the air interfaced surface of the cell layers. The transfer rate of BDP across the cell layer after deposition of the glycerol-free particles was proportional to the mass deposited. In comparison, the transfer of BDP from the glycerol-containing formulation was independent of the mass deposited, suggesting that the release of BDP is modified in the presence of glycerol. The rate of BDP transfer (and the extent of metabolism) over 2h was faster when delivered in glycerol-free particles, 465.01ng±95.12ng of the total drug (20.99±4.29%; BDP plus active metabolite) transported across the cell layer, compared to 116.17ng±3.07ng (6.07±0.16%) when the equivalent mass of BDP was deposited in glycerol-containing particles. These observations suggest that the presence of glycerol in the maturated aerosol particles may influence the disposition of BDP in the lungs.

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

UNLABELLED: 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.

Pseudomonas aeruginosa infection among cystic fibrosis and ICU patients in the referral children medical hospital in Tehran, Iran.

INTRODUCTION: Pseudomonas aeruginosa is one of the important causes of hospital-acquired infections in Intensive Care Unit (ICU) and considered as a major determinant of morbidity and mortality in patients affected by cystic fibrosis (CF). The aim of this study was to investigate clonal diversity among randomly picked P. aeruginosa isolates of CF and the other hospitalized patients in ICU. METHODS: Cultivation, identification, and antimicrobial susceptibility testing of P. aeruginosa isolates were performed using standard techniques. The genetic similarity of the strains was investigated by amplification of the Enterobacterial Repetitive Intergenic Consensus-polymerase chain reaction (ERIC-PCR) sequence. RESULTS AND DISCUSSION: Among 49 isolates, sixteen were isolated from 11 patients affected by CF and 33 came from an epidemiological investigation of 25 P. aeruginosa infected patients of ICU. Five clusters were generated for all isolates analyzed through ERIC-PCR genotyping. Two major clusters (B and C) were discovered in P. aeruginosa isolates of ICU and CF patients during the whole period of this study. Fifteen unique antibiogram patterns obtained from all isolates and multi-resistant P. aeruginosa (MRPA) were identified in 23 isolates (47%). MRPA isolates were detected in all clusters (except A) while pan-resistant isolates were recovered only in cluster C. The high prevalence of related or identical isolates in CF and non-CF patients can be due to transmission of particular dominant clones in ICU ward. Therefore, enhanced infection-control may become necessary to prevent further spread of clonal strains.

Epidemiological data, outcome, and costs of burn patients in Kermanshah.

Burn injuries in both developed and developing countries cause long-term disability, mortality, and socio-economic costs that are imposed on patients, families, and societies. This study was carried out to investigate the epidemiology, outcome, and cost of hospitalization of 388 burn patients admitted to the Imam Khomeini Hospital Burn Center in Kermanshah, Iran, between 21 March 2011 and 20 March 2012. The data about demographics, cause of burns, degree of burns, outcome of burns, burned body surface (BBS), length of stay (LOS), and cost of hospitalization were collected by reviewing medical records and analysed by SPSS 16. The patients' mean age was 27 years. The male/female ratio in burn patients was 1.14/1. The mean BBS was 36.06%. The mean LOS was 9.04 days. Flame (67.0%) and hot liquids (21.9%) were the major causes of burn. Burn injuries were more common in the upper limbs (81.4%), lower limbs (70.9%), and head and neck (65.2%). 11.6% of patients had all the regions involved. The fatality rate was 18.8%. The mean cost per patient was 20,463,227 Iran Rials (IRR). The cost per one percentage of burn and one day of hospitalization was 562,632 IRR and 2,263,631 IRR, respectively. The main factors relevant to death were identified including the extent of burn, gender, age, causes, and degree of burn. In addition, LOS proved to have a higher impact on costs than burn percentage.

Les brûlures, soit dans les pays développés soit dans ceux en développement, causent des invalidités à long terme, des décès et des coûts socioéconomiques imposés aux patients, aux familles et aux sociétés. Cette étude a été réalisée pour évaluer les résultats et les coûts de l'hospitalisation de 388 patients brûlés admis au Centre des Brûlés chez l'hôpital Imam Khomeini à Kermanshah, Iran, entre le 21 mars 2011 et le 20 mars 2012. Les données sur les caractéristiques démographiques, les causes des brûlures et leur degré, les résultats finaux, la surface corporelle brûlées (SCB), la durée du séjour hospitalier (DSH) et le coût de l'hospitalisation ont été recueillies moyennant l'examen des dossiers médicaux et analysées par SPSS 16. L'âge moyen des patients était de 27 ans. Le sex ratio homme / femme chez les patients brûlés était de 1,14/1. La SCB moyenne était de 36,06%. La DSH moyenne était de 9,04 jours. Les flammes (67,0%) et les liquides chauds (21,9%) étaient les principales causes des brûlures, qui se produisaient avec majeure fréquence aux membres supérieurs (81,4%), aux membres inférieurs (70,9%) et à la zone tête/cou (65,2%). Dans 11,6% des cas toutes les régions corporelles étaient intéressées. Le taux de la mortalité était de 18,8%. Le coût moyen par patient était de 20.463.227 Rials iraniens (IRR). Le coût par point de pourcentage de brûlure et par journée d'hospitalisation était de 562.632 IRR et de 2.263.631 IRR, respectivement. Les principaux facteurs pertinents à la mort ont été identifiés, notamment l'extension de la brûlure, le sexe, l'âge, les causes et le degré de brûlure. En outre, nous avons trouvé que la DSH causait un impact plus important sur les coûts que le pourcentage de brûlure.