Simulation of cancer progression in bone by a virtual thermal flux with a case study on lumbar vertebrae with multiple myeloma.

BACKGROUND: Two main problems examining the mechanism of cancer progression in the tissues using the computational models are lack of enough knowledge on the effective factors for such events in vivo environments and lack of specific parameters in the available computational models to simulate such complicated reactions. METHODS: In this study, it was tried to simulate the progression of cancerous lesions in the bone tissues by an independent parameter from the anatomical and physiological characteristics of the tissues, so to degrade the orthotropic mechanical properties of the bone tissues, a virtual temperature was determined to be used by a well-known framework for simulation of damages in the composite materials. First, the reliability of the FE model to simulate hyperelastic response in the intervertebral discs (IVDs) and progressive failure in the bony components were verified by simulation of some In-Vitro tests, available in the literature. Then, the progression of the osteolytic damage was simulated in a clinical case with multiple myeloma in the lumbar vertebrae. RESULTS: The FE model could simulate stress-shielding and diffusion of lesion in the posterior elements of the damaged vertebra which led to spinal stenosis. The load carrying shares associated with the anterior half and the posterior half of the examined vertebral body and the posterior elements were estimated equal to 41 %, 47 % and 12 %, respectively for the intact condition, that changed to 14 %, 16 % and 70 %, when lesion occupied one third of the vertebral body. CONCLUSION: Correlation of the FE results with the deformation shapes, observed in the MRIs for the clinical case study, indicated appropriateness of the procedure, proposed for simulation of the progressive osteolytic damage in the vertebral segments. The future studies may follow simulation of tumor growth for various metastatic tissues using the method, established here.

CARDIOPROTECTIVE EFFECT OF DICHLOROMETHANE VALERIAN (VALERIANA OFFICINALIS) EXTRACT ON ISCHEMIA-REPERFUSION-INDUCED CARDIAC INJURIES IN RATS.

Background: Valepotriate is an active ingredient of valerian (Valeriana officinalis) with strong antioxidant activity that is effective for numerous cardiovascular diseases. Objective: The aim of this study was to investigate the effect of an active ingredient of V. officinalis extract on ischemia-reperfusion-induced cardiac injuries in male rats. Methods: Thirty-two male rats were subjected to ischemia for 40 minutes and reperfusion for five days. The rats were divided into 4 groups of 8 each; group 1 (control) was given normal saline, and groups 2-4 were gavaged with 0.2, 0.1, 0.05 mg/kg of valepotriate extract, respectively, and received extract (0.2 mg/kg ip) two weeks before ischemia induction. Results: Dichloromethane V. officinalis (valepotriate) extract exerted a protective effect against ischemia-reperfusion-induced injuries. So that infarct size and number of ventricular arrhythmia and ventricular escape beats decreased compared to the control group. Moreover, ST segment amplitude, QTC interval, and heart rate decreased in the injured hearts and serum levels of antioxidant enzymes glutathione peroxidase, catalase, and superoxide dismutase increased. Biochemical markers malondialdehyde and lactate dehydrogenase also decreased on day 5 after the onset of reperfusion. Conclusion: V. officinalis extract may have a protective effect against myocardial ischemia-reperfusion by producing antioxidant effects.

Investigation of the Effect of PEG Detoxification on Diphtheria Vaccine.

Immunization has been considered a successful global health program that saves many persons' lives each year. The vaccines reduce the risk of getting the disease by building immunity in the body. Therefore, the constant availability of essential vaccines is an important factor in community health. One of the most important vaccines is the diphtheria vaccine, which is usually used as Multivalent diphtheria-tetanus-pertussis (DTP) combination vaccines. The production of this vaccine takes about 45 days, from the initial bacterial culture to the end of toxin production. However, the production of this vaccine can be optimized in case the production stages are carried out under normal conditions. In this study, a significant amount of impurities was removed after washing with phosphate buffer saline, and the toxin was then purified by Sephadex G-50. In this method, the toxin was concentrated to be stored in a smaller space (this removes the concerns for the provision of a suitable space). Another problem with the diphtheria vaccine is that it is reversible after detoxification of the toxin using formaldehyde. For this reason, it is suggested to use MPEG for detoxification, which will produce more stable covalent bonds between PEG and the first type of amine groups in the toxin chain. Tests were performed to evaluate factors, such as in vivo cytotoxicity, lack of edemas formation, the neutralizing activity of serum from guinea pigs immunized with the diphtheria toxoid inactivated with MPEG, and the immunogenic activity of the purified and modified toxin. Comparison of this PEG detoxification toxoid with the standard toxoid produced in Razi Vaccine and Serum Institution, Karaj, Iran, showed that washing with PBS and purification with Sephadex G-50 was an efficient method. The stability and reversibility of the toxoid approved by MPEG were acceptable. Therefore, the results of animal tests showed that the obtained product was stable and caused no wound or necrosis in the tested animals.

Proteome Analysis of Toxic Fractions of Iranian Cobra (Naja naja Oxiana) Snake Venom Using Two-Dimensional Electrophoresis and Mass Spectrometry.

Snake venoms are mostly composed of various proteins and peptides with toxicity and pharmacological effects depending on their geographical sources. Naja naja oxiana is one of the most medically important venomous snakes in Iran and Central Asia. The bite of this type of snake can cause severe pain and swelling, as well as neurotoxicity. Without medical treatment, symptoms quickly worsen and death can occur soon. A detailed understanding of venom components can provide new insight into the production of antivenom against toxic agents instead of crude venom. Specific antibodies against toxic fractions are of utmost importance in neutralizing crude venom. Therefore, the proteome profile of these fractions of Naja naja oxidana venom was analyzed using fractionation by gel filtration, two-dimensional electrophoresis, mass spectrometry, and data mining. Base on the results, in total, 32 spots were detected and categorized into three protein families, namely three-finger toxin (3FTx), phospholipase, and Cysteine-rich secretory proteins (CRISP). These proteins consist of more than 70% crude venom all with a molecular weight below 25 kDa. The 3FTx as a highly diverse constituent in the venom of Naja species was in large quantity in this district. Short-chain neurotoxins, including short neurotoxin, cytotoxin, and muscarinic toxin-like protein, were in abundance, respectively. In conclusion, the recognition of toxic fractions of Naja naja oxiana in this region could be of great help in the production of an effective antivenom against similar compositions. It can also help the medical care department to find out the clinical sign of cobra venom. To the best of our knowledge, this was the first study to report the proteomic of toxic fractions of Naja naja oxiana in Iran.

Using Apelin and exercise to protect the cardiac cells: synergic effect in ischemia reperfusion injuries treatment in rats.

AIM: Apelin is an active endogenous peptide, which affects blood vessels. Also exercise increases angiogenesis after myocardial infarction and exerts cardio protective effects. The aim of the present study was to investigate the effect of Apelin and aerobic exercise on reducing the severity of Ischemia-reperfusion injury in rats. METHODS: The rats were divided into the following 4 groups 8 weeks before surgery (Langendorff model of perfusion): I) Ischemia-reperfusion (I/R), II: Exercise Ischemia- reperfusion (EX+I/R), III: Apelin+Ischemia-reperfusion (APE+I/R) (Apelin 10 nmol/kg/day, i.p), and IV: Exercise+Apelin+Ischemia-reperfusion (EX+APE+I/R). Exercise was performed on a treadmill 8 weeks before the surgery at a speed of 17 m/min for 10 to 50 min/day. The ventricular function was evaluated after I/R injury, histopathological and immunohistopathology indices were then measured at the scar tissue. RESULTS: The results of H(et)E, Masson's trichrome staining indicated that APE+EX pre-treatment reduced cardiac fibrosis and the percentage of collagen deposition. It also enhanced the microvessels density (MVD) and decreased the number of inflammatory cells and apoptosis rate. CONCLUSION: According to our study, Apelin and exercise preconditioning had anti-fibrotic and anti-apoptotic effects on the ischemia-reperfusion myocardium cells, which could lead to the protection of cardiac cells (Tab. 5, Fig. 3, Ref. 33).

Isolation and confirmation of viral nervous necrosis (VNN) disease in golden grey mullet (Liza aurata) and leaping mullet (Liza saliens) in the Iranian waters of the Caspian Sea.

The present study was conducted on 428 moribund mullet fish samples to isolate and identify the causative agent of a mysterious acute mortality which recently occurred in wild mullets in Iranian waters of Caspian Sea, suspected to be due to viral nervous necrosis (VNN) disease. Disease investigation was carried out employing various diagnostic procedures such as virology, bacteriology, parasitology, haematology, histopathology, IFAT, IHC and nested RT-PCR. Brain and eye samples of affected fishes were collected in sterile conditions and then kept at -80°C for cell culture isolation and nested RT-PCR detection of the causative agent. Other tissue samples were also collected and fixed for histopathology, IHC and EM examinations. CPE was observed in cell cultures at 6days after inoculation. Nine samples were found positive with virological assay. Nested RT-PCR, performed on suspected tissues and CPE positive samples, showed that about 21 tissue samples and all the CPE positive samples were positive for VNN virus (VNNV). IFAT was selected as a confirmatory method for detecting the presence of Betanodavirus antigen, cell culture isolation results and nested RT-PCR findings. Moreover, VNNV particles with 25-30nm in diameter were also visualized in the infected brain and retina. In pathogenicity studies, guppy fishes bathed in VNNV-infected tissue culture (10(-4) TCID50) showed clinical signs similar to naturally infected mullet after 15days post infection (dpi), with mortality rates reaching up to 100% at 30dpi. Affected organ samples as examined by cell culture isolation, IFAT, IHC and histopathology, revealed the presence of VNNV in the guppy fishes. In conclusion, it was confirmed that VNNV was the main causative agent for the disease outbreak in mullet fish in the Caspian Sea, and this is such first official report of VNN disease from Iran.

Chemical composition and hepatoprotective activity of ethanolic root extract of Taraxacum Syriacum Boiss against acetaminophen intoxication in rats.

AIM: In the present study, the role of ethanol extract of root of Taraxacum Syriacum Boiss (TSBE) against hepatotoxicity caused by acetaminophen (APAP) was studied. METHODS: The chemical composition of roots of Taraxacum Syriacum Boiss was analyzed by SPME-GC/MS method. Hepatocellular injuries induced by acetaminophen (APAP) were assessed by liver histology, serum aminotransferase activities, antioxidant enzymes activity and lipid peroxidation in liver tissue. RESULTS: TSBE was observed to exhibit hepatoprotective effect as demonstrated by significant decrease in serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), and alkaline phosphatase (ALP) concentration, and by preventing liver histopathologic changes in rats with APAP hepatotoxicity. Administration of APAP, significantly increased, lactate dehydrogenase (LDH) and catalase (CAT) activity in liver tissue and pretreatment with TSBE returned these parameters to control group, moreover TSBE reduces APAP-induced hepatic Glutathione (GSH) depletion. Carvacrol (6.7 %) was the main polyphenolic compound of plant sample. Our results demonstrated hepatoprotective activity of TSBE in rat in vivo. CONCLUSIONS: We believe that the mechanism by which the extract was able to protect the liver from the oxidative stress generated by APAP is due to its antioxidant activity. These phenolic compounds of the extract act as antioxidants and free radical scavengers and reduce or inhibit the oxidative stress induced by APAP administration (Tab. 3, Fig. 3, Ref. 39).

An inset CT specimen for evaluating fracture in small samples of material.

In evaluations on the fracture behavior of hard tissues and many biomaterials, the volume of material available to study is not always sufficient to apply a standard method of practice. In the present study an inset Compact Tension (inset CT) specimen is described, which uses a small cube of material (approximately 2×2×2mm(3)) that is molded within a secondary material to form the compact tension geometry. A generalized equation describing the Mode I stress intensity was developed for the specimen using the solutions from a finite element model that was defined over permissible crack lengths, variations in specimen geometry, and a range in elastic properties of the inset and mold materials. A validation of the generalized equation was performed using estimates for the fracture toughness of a commercial dental composite via the "inset CT" specimen and the standard geometry defined by ASTM E399 (2006). Results showed that the average fracture toughness obtained from the new specimen (1.23±0.02MPam(0.5)) was within 2% of that from the standard. Applications of the inset CT specimen are presented for experimental evaluations on the crack growth resistance of dental enamel and root dentin, including their fracture resistance curves. Potential errors in adopting this specimen are then discussed, including the effects of debonding between the inset and molding material on the estimated stress intensity distribution. Results of the investigation show that the inset CT specimen offers a viable approach for studying the fracture behavior of small volumes of structural materials.

Body dysmorphic factors and mental health problems in people seeking rhinoplastic surgery.

There has been increasing number of requests for cosmetic rhinoplastic surgery among Iranian people in different age groups in recent years. One risk for people who undergo such plastic operations is the presence of body dysmorphic disorder (BDD), which can complicate the result and decrease the rate of satisfaction from surgery. This study aimed to investigate mental health problems in people seeking rhinoplastic surgery. In this case-control study, the scores of General Health Questionnaire (GHQ) and DCQ (Dysmorphic Concerns Questionnaire) were obtained from 50 individuals who were candidates for rhinoplasty, and the results were compared with a normal control group. The total GHQ score and scores in anxiety, depression, and social dysfunction sub-scales were higher among the study group. This was the same for the DCQ score. However, the scores of somatization sub-scale of GHQ were not significantly different between the two groups. Psychiatric evaluation of candidates for rhinoplasty seems necessary for prevention of unnecessary and repetitive surgical operations.

Skew in the human caveolin 1 gene upstream purine complex homozygote haplotype compartment in multiple sclerosis.

Caveolin 1 (CAV1) is a component of the myelin sheath and the expression of the gene encoding this protein is increased during myelination in Schwann cells and oligodendrocytes. We sought to investigate the homozygote haplotype compartment in a recently identified polymorphic purine complex at the upstream region of the human CAV1 gene in multiple sclerosis (MS). In a case/control study design, the region was characterized in 126 cases of MS diagnosed based on the Revised McDonald diagnostic criteria, and 460 controls. We report a skew in the homozygote haplotype compartment in the cases versus controls both in a qualitative and quantitative respect. Excess homozygosity for haplotypes was observed in the MS cases (corrected p<0.012, OR=2.54, CI 1.14-5.64). Furthermore, we observed eight homozygote haplotypes in the MS cases that were non-existent in the controls (p<0.0003, OR=20.27, CI 2.50-163.8). For the first time, our data highlight the CAV1 upstream purine complex as a novel susceptibility genomic locus in the pathophysiology of MS. Of utmost importance, the region has been conserved across species, including mouse, guinea pig, rhesus macaque, and human. The functional effect of this region remains to be clarified in the future studies.

Aging and the reduction in fracture toughness of human dentin.

An evaluation of the crack growth resistance of human coronal dentin was performed on tissue obtained from patients between ages 18 and 83. Stable crack extension was achieved over clinically relevant lengths (0< or = a < or =1mm) under Mode I quasi-static loading and perpendicular to the nominal tubule direction. Results distinguished that human dentin exhibits an increase in crack growth resistance with extension (i.e. rising R-curve) and that there is a significant reduction in both the initiation (K(o)) and plateau (K(p)) components of toughness with patient age. In the young dentin (18< or =age< or =35) there was a 25% increase in the crack growth resistance from the onset of extension (K(o)=1.34 MPa m(0.5)) to the maximum or "plateau" toughness (K(p)=1.65 MPa m(0.5)). In comparison, the crack growth resistance of the old dentin (55< or =age) increased with extension by less than 10% from K(o)=1.08 MPa m(0.5) to K(p)=1.17 MPa m(0.5). In young dentin toughening was achieved by a combination of inelastic deformation of the mineralized collagen matrix and microcracking of the peritubular cuffs. These mechanisms facilitated further toughening via the development of unbroken ligaments of tissue and posterior crack-bridging. Microstructural changes with aging decreased the capacity for near-tip inelastic deformation and microcracking of the tubules, which in turn suppressed the formation of unbroken ligaments and the degree of extrinsic toughening.

Effect of the degree of fragmentation on embryo survival after freeze-thawing.

PURPOSE: To determine if the degree of fragmentation of embryos prior to freezing correlate in a negative manner with survival after thawing. METHODS: A retrospective review of frozen embryos thawed for purposes of embryo transfer was done. Survival and transferability rates were determined according to degree of fragmentation. RESULTS: The chance that an embryo with < 25% fragmentation was deemed good enough for transfer upon thawing was 63.6% compared to 52.8% for embryos > 25% (p < .05). CONCLUSIONS: Though more fragmented embryos have a lower survival rate after freeze thawing, about 50% of embryos with > 25% fragmentation will still survive the thaw and be able to be transferred.

Power of microsatellite markers for analysis of genetic variation and parentage verification in sheep.

We report the genetic analysis of 100 individuals of an elite breeding flock of Afshari sheep with a selected set of eighteen microsatellite markers. A full characterization of this set of eighteen loci was carried out generating allele frequency distributions that were used to estimate the genetic information content of these loci, including genetic variability, inbreeding, individual and parent verification parameters. Disregarding MCMA26 monomorphic pattern, microsatellite loci showed moderate level of polymorphism, as such totally 102 alleles were detected with a mean number of 6 alleles per locus. The average expected heterozygosity was 0.72 (SD = 0.07) and the average Polymorphism Information Content (PIC) was 0.67 (SD = 0.08). Total value of inbreeding based on marker data was estimated as -0.02 so it indicates that inbreeding occurred less than would be expected at random. The overall probability of identity considering all twelve independent loci combined was 3.148E-13 meaning lower than 1 in 31 trillions. The results of this study indicate, despite the selective breeding and closed flock system over a number of generations, a relatively high level of heterozygosity still exists in the representative sheep flock. The high degree of multiallelism and the clear and simple codominant Mendelian inheritance of the set of microsatellites used provide a powerful system for the unique identification of Afshari sheep individuals for fingerprinting purposes and parentage testing.

Ectopic pregnancy is not more likely following fresh vs frozen embryo transfer.

PURPOSE: To determine if the risk of ectopic pregnancy is greater following frozen vs fresh embryo transfer (ET). METHODS: Retrospective review of pregnancy outcome from January 1, 1997 to November 30, 2003. Cryopreservation was used as a simple freezing method and one-step removal of cryoprotectant. The cycles consisted mostly of graduated estradiol and progesterone supplementation. RESULTS: The ectopic pregnancy rate in 1,445 clinical pregnancies from fresh ET was 2.6% vs 2.0% of 975 clinical pregnancies resulting from frozen ET. CONCLUSION: In contrast to the conclusions of two previous studies, the present study evaluating twice as many clinical pregnancies than the two aforementioned studies combined failed to show any greater risk of ectopic pregnancy when transfers were performed on day 3.

Non-homogeneous hyperechogenic echo pattern three days after frozen embryo transfer is associated with lower pregnancy rates.

OBJECTIVE: To evaluate the association of mid-luteal phase echo patterns and pregnancy rates (PRs) following frozen embryo transfer (ET). METHODS: Sonographic evaluation of endometrial echo patterns was performed three days after ET in the first frozen ET cycle of women < 40 years of age who used their own oocytes as well as all donor oocyte recipients. RESULTS: The distribution of echo patterns and clinical PRs were similar in women using their own eggs and women who used donor oocytes; therefore all data was combined. The clinical PR was 49.5% with a hyperechogenic echo pattern vs 38.8% with a non-hyperechogenic pattern, p = .007. CONCLUSION: A larger study of frozen ET and mid-luteal echo pattern now demonstrates conclusions similar to the data from fresh ET in hyperstimulated in vitro fertilization (IVF)-ET cycles in that failure to attain a hyperechogenic echo pattern three days after ET is associated with lower pregnancy rates.

Possible mechanism(s) for relaxant effects of Foeniculum vulgare on guinea pig tracheal chains.

In a previous study the relaxant (bronchodilatory) effect of Foeniculum vulgare on isolated guinea pig tracheal chains was demonstrated. To study mechanisms responsible for this effect the present study evaluated the inhibitory effect of this plant on contracted tracheal chains of guinea pig. The relaxant effects of aqueous and ethanol extracts and an essential oil from Foeniculum vulgare were compared to negative controls (saline for aqueous extract and essential oil and ethanol for ethanol extract) and a positive control (diltiazem) using isolated tracheal chains of the guinea pig precontracted by 10 microM methacholine (group 1) and 60 mM KCl (group 2, n = 7 for each group). In the group 1, experiments diltiazem, ethanol extract, and essential oil from Foeniculum vulgare showed a significant relaxant effect on methacholine induced contraction of tracheal chains compared to those of negative controls (p < 0.05 to p < 0.001). In addition the effect of the ethanol extract was significantly greater than that of diltiazem (p < 0.001). However, the aqueous extract did not show any relaxant effect in group 1. In the group 2 experiments, only diltiazem showed a significant relaxant effect on KCl induced contraction of tracheal chains (p < 0.001). The relaxant effects of ethanol extracts and essential oil obtained in the group 2 experiments were significantly lower than those in group 1 (p < 0.05 to p < 0.001). These results confirm the bronchodilatory effects of ethanol extract and essential oil from Foeniculum vulgare. However with regard to the effect of KCl on calcium channels, the results indicated that the inhibitory effect of ethanol extracts and essential oil from Foeniculum vulgare on calcium channels is not contributing to their relaxant (bronchodilatory) effects on guinea pig tracheal chains. However the results suggest a potassium channel opening effect for this plant, which may contribute on its relaxant effect on guinea pig tracheal chains.

Neither sildenafil nor vaginal estradiol improves endometrial thickness in women with thin endometria after taking oral estradiol in graduating dosages.

PURPOSE: To determine if sildenafil improves endometrial thickness better than vaginal estradiol (E2) in women with a history of thin endometria. METHODS: Women failing to attain an 8 mm endometrial thickness on either the oocyte retrieval cycle or their first frozen embryo transfer (ET) despite an oral graduated E2 regimen were treated again with graduated oral E2 and were also randomly assigned to vaginal sildenafil or vaginal E2 therapy. Endometrial thickness was compared between the groups. RESULTS: Neither vaginal E2 nor sildenafil significantly improved endometrial thickness or blood flow in the subsequent frozen ET-cycle. CONCLUSIONS: These data fail to corroborate previous claims that 25 mg sildenafil four times daily intravaginally can improve endometrial thickness.

Live birth after posthumous testicular sperm aspiration and intracytoplasmic sperm injection with cryopreserved sperm: case report.

PURPOSE: To determine if a viable pregnancy is possible after aspiration of sperm from the testes of a man several hours after his death. METHOD: Following cryopreservation of the aspirated sperm, in vitro fertilization (IVF)-embryo transfer (ET) with intracytoplasmic sperm injection (ICSI) was used. The sperm selected were either those with motility or plumper non-motile sperm. RESULTS: Fertilization of oocytes and ET occurred following all five IVF-ET cycles. A clinical pregnancy was achieved in cycle 1 with non-motile sperm and a viable pregnancy resulted from cycle 5 with ICSI performed with viable sperm. CONCLUSION: Viable pregnancies following IVF-ET and ICSI are possible even when using testicular sperm obtained posthumously.

The importance of number of blastomeres when embryos are transferred in the absence of controlled ovarian hyperstimulation.

PURPOSE: To determine if the previous findings that transferring embryos with a higher number of blastomeres results in higher pregnancy rates following fresh but not frozen embryo transfer (ET) was related to the use of controlled ovarian hyperstimulation (COH) in the former but not in the latter. METHODS: Retrospective review of pregnancy and implantation rates following fresh embryo transfer of donor egg recipient cycles (where no COH is used) vs frozen ETs during the same time period according to whether there was at least one embryo with eight blastomeres transferred or not. RESULTS: Significantly higher pregnancy rates with an 8-cell ET in donor oocyte recipient cycles but not frozen ETs. CONCLUSIONS: A less favorable uterine environment caused by the use of high dose gonadotropin is not responsible for the once again observed difference in higher pregnancy rates with higher blastomere number in fresh vs frozen ET. However, an effect of the gonadotropin releasing hormone analogue was not ruled out by this study.