Simulation of Respiratory Mechanics

The dynamic relationship between respiratory muscle effort and the consequent changes in lung volume is investigated. A mathematical simulation based on the structures that form the connection between these two variables makes it possible to lump the contribution from all respiratory muscles into a single time-varying driving force. When this force is applied to the system model, the appropriate lung volume pattern results. The simulation results indicate the accuracy of the model and the validity of the lumped muscle force assumption. In addition, the system model adequately describes abnormal conditions such as decreased lung compliance and increased airway resistance. The results of this simulation suggest that the modeling technique is extremely useful in describing and analyzing complex respiratory system interactions.     

Synaptosomal Na+,K+-ATPase as a membrane probe in studying the in vivo action of morphine

The activity of membrane-bound Na+,K+-ATPase was used as a metabolic probe to study the effects of morphine in vivo in rat brain synaptosomes. Arrhenius plots were generated to study an induced perturbation within the membrane. In acute studies 0.5-h postmorphine, the drug was without effect on the basal activity of the enzyme. With dopamine-stimulated Na+,K+-ATPase morphine decreased the apparent transition temperature and specific activity of the enzyme while there was a slight stimulation in its activation energy. An increase in these parameters was observed in samples taken from animals withdrawn from the drug for 48 h. These results strongly suggest the possible involvement of the membrane phospholipids as transducer which mediates the observed biphasic effect of the drug on enzyme activity.     

Analysis of HLA DR2&;DQ6 (DRB1*1501, DQA1*0102, DQB1*0602) Haplotypes in Iranian Patients with Multiple Sclerosis

Multiple sclerosis (MS) is prototype of inflammatory demyelinating disease of the central nervous system .The etiology of MS remains unclear, but according to current data the disease develops in genetically susceptible individuals and may require additional environmental triggers. The human leukocyte antigen (HLA) class II alleles (DRB1*1501, DQA1*0102, DQB1*0602) may have the strongest genetic effect in MS. In this study, the role of these alleles were investigated in 183 Iranian patients with multiple sclerosis and compared with 100 healthy individuals. HLA typing for DRB1*1501, DQA1*0102, DQB1*0602 was performed by polymerase chain reaction (PCR) amplification with sequence-specific primers (PCR-SSP) method. The results show that, HLA DR B1*1501 was significantly more frequent among MS patients (46% vs. 20%, PV = 0.0006) but DQA1*0102 haplotype was negatively associated with MS (30% vs. 50%, PV = 0.0049) and no significant association was found with DQB1*0602 and MS patients in comparison with control group (24% and 30%, PV = 0.43). No significant correlation was observed among these alleles with sex, type of disease; initial symptoms, expanded disability status scale (EDSS), as well as age at onset and familial MS. This study therefore indicates that there is no association of above HLA haplotypes with clinical presentation, disease duration, and disability in Iranian patients with MS which is in line with other previous studies in different ethnic groups.     

An extracellular source of heme can induce a significant heme oxygenase mediated relaxation in the rat aorta

Carbon monoxide has been under active investigation for a role in controlling vascular tone throughout the last decade because of its ability to induce relaxation in blood vessels. The underlying mechanisms of this response are hypothesized to be mediated by soluble guanylyl cyclase (sGC) and, in some instances, KCa channels. The major source of CO in major blood vessels is the catabolic process of heme degradation, which is catalyzed by heme oxygenase (HO). This heme substrate could be derived from heme sources within vascular smooth muscle cells, such as heme proteins, or by uptake from the extracellular milieu. The current study shows that the isolated rat aorta relaxes upon exposure to pharmacological concentrations of heme in the bathing medium. This response was inhibited by an inhibitor of HO (tin protoporphyrin) and sGC (1-H-[1,2,4]-oxadiazolo[4,3-a]quinoxalin-1-one). These observations were interpreted to mean that vascular smooth muscle cells are capable of taking up and utilizing heme for the production of CO.     

Time course of the hepatic adaptation to TPN: interaction with glycogen depletion

In response to chronic (5 days) TPN, the liver becomes a major site of glucose disposal, removing approximately 45% (4.5 mg.kg(-1).min(-1)) of exogenous glucose. Moreover, approximately 70% of glucose is not stored but released as lactate. We aimed to determine in chronically catheterized conscious dogs the time course of adaptation to TPN and the glycogen depletion impact on early time course. After an 18-h (n = 5) fast, TPN was infused into the inferior vena cava for 8 (n = 5) or 24 h (n = 6). A third group, of 42-h-fasted animals (n = 6), was infused with TPN for 8 h. TPN was infused at a rate designed to match the dog's calculated basal energy and nitrogen requirements. NHGU (-2.3 +/- 0.1 to 2.2 +/- 0.7 to 3.9 +/- 0.6 vs. -1.7 +/- 0.3 to 1.1 +/- 0.5 to 2.9 +/- 0.4 mg.kg(-1).min(-1), basal to 4 to 8 h, 18 vs. 42 h) and net hepatic lactate release (0.7 +/- 0.3 to 0.6 +/- 0.1 to 1.4 +/- 0.2 vs. -0.6 +/- 0.1 to 0.1 +/- 0.1 to 0.8 +/- 0.1 mg.kg(-1).min(-1), basal to 4 to 8 h) increased progressively. Net hepatic glycogen repletion and tracer determined that glycogen syntheses were similar. After 24 h of TPN, NHGU (5.4 +/- 0.6 mg.kg(-1).min(-1)) and net hepatic lactate release (2.6 +/- 0.4 mg.kg(-1).min(-1)) increased further. In summary, 1) most hepatic adaptation to TPN occurs within 24 h after initiation of TPN, and 2) prior glycogen depletion does not augment hepatic adaptation rate.     

Association of Htra1 gene polymorphisms with the risk of developing AMD in Iranian population

Background:

Half of the cases of vision loss in people under 60 years of age have been attributed to age-related macular degeneration (AMD). This is a multifactorial disease with late onset. It has been demonstrated that many different genetic loci are implicated in the risk of developing AMD in different populations. In the current study, we investigated the association of high-temperature ‎requirement A-1 (HTRA1) gene polymorphisms with the risk of developing AMD in the Iranian population.

Methods:

Genomic DNA samples were extracted from 120 patients with AMD and 120 healthy age- and sex-matched controls. A 385 base-pair fragment of the HTRA1 gene promoter region was amplified using the polymerase chain reaction (PCR) technique and sequenced. The frequencies of the alleles were calculated and statistical analysis was performed using SPSS software.

Results:

Our study demonstrated that the rate of polymorphisms rs11200638 -625 G>A and rs2672598 -487T>C were significantly greater in AMD patients than in healthy controls from the Iranian population.

Conclusions:

The results of our study indicate that HTRA1 gene promoter region polymorphisms are associated with the risk of developing AMD in the Iranian population.Key Words: HTRA1, Single Nucleotide Polymorphisms, Macular Degeneration, Iran