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Histamine participates in a variety of physiological functions. The local effects of histamine have a role to provide metabolic energy for the tissues. The objective of this work is to study the mechanism whereby histamine affects serum glucose and liver glycogen fractions. Six groups of 10 male rats received two injections with histamine, H1-agonist (dipyridylethylamine), H2-agonist (dimaprit), H1-agonist plus H1-antagonist (cetirizine), or H2-agonist plus H2-antagonist (famotidine). Serum glucose and liver glycogen fractions were measured. Histamine caused a significant increase in serum glucose (163.7 ± 5.4 vs. 153.2 ± 3.3 mg/dl, p = 0.023). The effect of histamine was mimicked by selective H1-agonist (164.2 ± 3.5 vs. 152.8 ± 2.9 mg/dl, p = 0.005) but not with H2-agonist (159.3 ± 3.7 vs. 156.3 ± 4.8 mg/dl, p = 0.281). The effect of H1-agonist was abolished in the presence of selective H1-antagonist. Treatment by H1- but not H2-agonist decreased total glycogen by about 35% (30.6 ± 0.5 vs. 47.3 ± 2.8 mg/g wet weight of liver, p = 0.003). The decrease happened wholly in ASG fraction (26.8 ± 1.2 vs. 43.7 ± 3.2 mg/g wet weight of liver, p = 0.004), while AIG did not change significantly (4.2 ± 0.5 vs. 4.5 ± 0.4 mg/g wet weight of liver, p = 0.724). Histamine causes to decrease glycogen in the liver and increased serum glucose. The effects of histamine were mediated via H1-receptors. ASG was metabolically active fraction of liver glycogen in this process. The results confirm the role of histamine in providing metabolic energy of the tissues.

It has been almost 18 months since the first outbreak of COVID-19 disease was reported in Wuhan, China. This unexpected devastating phenomenon, raised a great deal of concerns and anxiety among people around the world and imposed a huge economic burden on the nations’ health care systems. Accordingly, clinical scientists, pharmacologists and physicians worldwide felt an urgent demand for a safe, effective therapeutic agent, treatment strategy or vaccine in order to prevent or cure the recently-emerged disease. Initially, due to the lack of specific pharmacological agents and approved vaccines to combat the COVID-19, the disease control in the confirmed cases was limited to supportive care. Accordingly, repositioning or repurposing current drugs and examining their possible therapeutic efficacy received a great deal of attention. Despite revealing promising results in some clinical trials, the overall results are conflicting. For this reason, there is an urgent need to seek and investigate other potential therapeutics. Mesenchymal stem cells (MSC), representing immunomodulatory and regenerative capacity to treat both curable and intractable diseases, have been investigated in COVID-19 clinical trials carried out in different parts of the world. Nevertheless, up to now, none of the MSC-based approaches has been approved in controlling COVID-19 infection. Thanks to the fact that the final solution for defeating the pandemic is developing a safe, effective vaccine, enormous efforts and clinical research have been carried out. In this review, we will concisely discuss the safety and efficacy of the most relevant pharmacological agents, MSC-based approaches and candidate vaccines for treating and preventing COVID-19 infection.

Background Critical limb ischemia (CLI) is associated with increased risk of tissue loss, leading to significant morbidity and mortality. Therapeutic angiogenesis using cell-based treatments, notably mesenchymal stem cells (MSCs), is essential for enhancing blood flow to ischemic areas in subjects suffering from CLI. The objective of this study was to evaluate the feasibility of using placenta-derived mesenchymal stem cells (P-MSCs) in patients with CLI. Methods This phase I dose-escalation study investigated P-MSCs in nine CLI patients who were enrolled into each of the two dosage groups (20 × 106 and 60 × 106 cells), delivered intramuscularly twice, two months apart. The incidence of treatment-related adverse events was the primary endpoint. The decrease in inflammatory cytokines, improvement in the ankle-brachial pressure index (ABI), maximum walking distance, vascular collateralization, alleviation of rest pain, healing of ulceration, and avoidance of major amputation in the target leg were the efficacy outcomes. Results All dosages of P-MSCs, including the highest tested dose of 60 × 106 cells, were well tolerated. During the 6-month follow-up period, there was a statistically significant decrease in IL-1 and IFN-γ serum levels following P-MSC treatment. The blood lymphocyte profile of participants with CLI did not significantly differ, suggesting that the injection of allogeneic cells did not cause T-cell proliferation in vivo. We found clinically substantial improvement in rest pain, ulcer healing, and maximum walking distance after P-MSC implantation. In patients with CLI, we performed minor amputations rather than major amputations. Angiography was unable to demonstrate new small vessels formation significantly. Conclusion The observations from this phase I clinical study indicate that intramuscular administration of P-MSCs is considered safe and well tolerated and may dramatically improve physical performance and minimize inflammatory conditions in patients with CLI. Trial registration: IRCT, IRCT20210221050446N1. Registered May 09, 2021.

Purpose Based on the resource-based view and dynamic capabilities theory, this study aims to examine the complementarity between market orientations and launch proficiency as a driver of new product performance. Design/methodology/approach In this research, an on-site survey of Iranian, research and development- intensive, manufacturing firms was carried out to examine the proposed hypotheses. Based on the 179 workable survey responses, a covariance-based structural equation modeling was applied to verify the proposed theoretical model. Findings The empirical findings reveal that the effects of market orientation or launch proficiency alone are not significant while the complementarity between them significantly influences new product performance. These research outcomes suggest that this complementarity leads to a bidirectional co-specialization relationship in firms, promoting both market intelligence generation processes and product-launch capabilities, and therefore resulting in superior new product performance. Originality/value The current characterization of the resource-based theory signifies that strategic resources merely have potential value and actualizing this value needs complementary organizational capabilities. Furthermore, the literature notably lacks empirical findings supporting these complementarities. Therefore, the findings concerning the bidirectional co-specialization between market orientation and launch proficiency not only provide empirical support for the dynamic capabilities theory but also address recent research calls to identify and calibrate the importance of dynamic capabilities for leveraging market orientation on new product performance.

Aim of the study The secretion rate of triglyceride from rat liver is assayed by the measurement of triglyceride accumulation in plasma when its clearance is inhibited. The aim of the study was to measure and compare the secretion rate of triglyceride from rat liver by two methods of fixed-time and continuous assays. Material and methods A single dose of 200 mg of poloxamer-407 (P-407) was injected i.p. into starved male rats. The secretion rate of triglyceride was measured by fixed-time and continuous assays. Results The time course for the changes of serum triglyceride following injection of P-407 showed three distinct phases: a lag period of about 30 minutes, a linear increase in serum triglyceride that lasted more than 4 hours, and a slight decline of triglyceride accumulation that lasted about 24 hours. The mean rate of triglyceride secretion was 234.1 ±9.6 mg/dl/h during the linear phase. The linear phase was divided into five time protocols of 240, 180, 120, 60, and 30 minutes and the secretion rate was measured at three points of time in each protocol. The mean rate of triglyceride secretion was 3.91 ±0.15, 3.83 ±0.16, 3.76 ±0.29, 3.57 ±0.43 and 3.13 ±0.34 mg/dl/min in these protocols respectively. In the kinetic assay, the change in the absorbance per three successive five minutes (ΔA/Δt) was measured and the secretion rate was calculated as 3.82 ±0.11 mg/dl/min. Conclusions The rate of triglyceride secretion can be measured by both fixed-time and kinetic assays and was about 3.82 ±0.11 mg/dl/min. The results of the two methods are more corresponded as the mean and instantaneous velocity respectively.

The research was performed to study the mechanism whereby histamine affects the profile of plasma lipids. Six groups of ten male rats were received two injections with histamine or its H1- and H2-agonists and antagonists. Histamine caused a significant decrease in the concentrations of triglyceride, total cholesterol, and LDLc, while HDLc had no significant change. The rate of VLDL secretion was 263.6 ± 25.8 mg/h dL in control rats and was inhibited by about 68% in histamine injected rats. These changes have been mimicked by either histamine H1- or H2-agonists. The effects of H1- and H2-agonists were abolished in the presence of cetirizine and famotidine respectively. Histamine causes a significant decrease in serum triglyceride, total, and LDL-cholesterol by both H1 and H2-receptors. The decrease in serum lipids is due to the inhibitory effect of histamine or its agonists on VLDL secretion from the liver.

We examine the impact of the macroeconomic determinants of foreign direct investment inflows. We also investigate the moderating role of sanctions in FDI inflows into Iran. The results reveal that macro determinants such as infrastructure, exchange rate, inflation rate, investment return, and governance have a long-run effect on FDI inflows in Iran. Our findings also show that GDP growth rate and trade openness have no significant effect on FDI. Our results indicate that sanctions do not have a significant moderating role in the relationship between macroeconomic factors and FDI. Surprisingly, international sanctions have a positive relationship with FDI inflows in Iran. Furthermore, sanctions have a positive impact on the inflation rate and exchange rate in Iran. Finally, our findings show that sanctions have had a significant impact on Iran’s economic growth in recent years due to increasing the severity level of sanctions.

Background: Cardiovascular disease (CVD), particularly coronary artery disease (CAD), constitutes the leading cause of death across the world. They are responsible for the highest mortality rate in Iran. The traditional risk factors for CAD are smoking, obesity, hypertension, family history, diabetes mellitus, and hyperlipidemia. Furthermore, enhanced oxidative stress is known as a novel risk factor for CAD. Objectives: The associations of oxidative and antioxidative markers were investigated relative to the occurrence and severity of CAD. Methods: A total of 286 participants, including 141 males and 145 females aged 30 - 70, were classified as CAD case and control groups, based on their coronary angiography results. The CAD severity scoring was done based on the number and extent of lesions in coronary arteries. The activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and Total antioxidant capacity (TAC) was assayed using the ferric reducing ability of plasma (FRAP) method. Meantime, malondialdehyde (MDA) was measured as a lipid peroxidation product. Results: The results demonstrated a significant increase in SOD activity (P = 0.019) and the uric acid concentration (P = 0.000) of CAD patients compared to the control group. Although no change was seen in GPx and CAT activity, as well as FRAP and MDA, a significant positive correlation was found between CAT and SOD activity (P = 0.011) and between FRAP and uric acid (P = 0.000) levels. Conclusions: The results suggest that some antioxidants are significantly associated with the severity of CAD, thereby helping predict the risk of cardiovascular events. However, extra studies are needed to endorse the significance of these findings.

The knowledge management orientations that firms adopt as a business input may lead at least partially to the superior performance of the new products they introduce to the market. Our empirical research investigates the knowledge management orientation effect on new product commercialization performance, using data collected from 700 Iranian manufacturing firms in six industries including plastic, steel manufacturing, construction, machinery, stone, mine, and Nano industries. However, our final sample due to missing data is 252 firms. Further, we study the mediating role of proactive and responsive market orientation. Our findings indicate that knowledge management orientation is positively associated with three aspects of new product commercialization, namely product advantage, new product development, and the number of new products introduced to the market. However, there was no significant mediating role in market orientation. Finally, our results show that market orientation and knowledge management orientation affect commercialization performance and therefore could improve new product commercialization.

The respiratory system is a complex group of organs in the human body, all of which are necessary in breathing. Due to its special anatomy and composition, after exposure to various damaging factors such as micro particles, carbon granules and toxic gases, the respiratory system can be affected by a variety of damage without return to its original state. Currently, the prevalence of lung diseases, including asthma, and chronic obstructive pulmonary diseases, such as emphysema, has increased remarkably. New therapeutic approaches are desperately needed to discover regenerative medicine approaches, especially cell therapy. This review summarizes the recent advances in stem cell treatments and the research efforts conducted through the application of stem cell therapy for respiratory system diseases. In particular, researchers have used animal models to gather data about treating lung injury by stem cell transplantation. This review concentrated on the findings about route, timing and adjustment of cell transplantation dose, optimum stem cell type selection and potency marker of cells as therapeutic agents. These factors are essential subjects for approval and clinical transplantation. The current clinical trials aiming at treatment of lung diseases by stem cells are mentioned and discussed.

Background. Brands are the most important source of emotional attachment with the consumer, it should be used as a vital tool for attracting and retaining customers of the organization and various sports organizations, should follow the theoretical principles related to brand management and brand loyalty and move towards strategic brand management as a superior marketing philosophy. Objectives. The purpose of this research was to position the Sport Sciences Research Institution of Iran using the Perceptual Mapping Technique. Methods. Competitive characteristics and strategic rivals of the Sport Sciences Research Institution were obtained from Rasooli Research (2013). Competitive characteristics and competitors were then prioritized using a researcher-made questionnaire and hierarchical method. The statistical population of this research consisted of the academic staff of the country including faculty members and graduate students. Analytic hierarchy analysis was used to prioritize the research variables. Results. Based on the obtained results, perceptual maps of the brand position of the research Center were depicted. The results showed that the position of brand of Sport Sciences Research Institution among academic researchers of the country in terms of research services, facilities and products was higher than other competitors while the field of educational services after physical education faculties was in the second place; and effort should be made in this area to promote their brand. Conclusion. In the competitive and turbulent environment of today, the role of brand as consumers' decision-making guide is becoming more important. Branding should therefore be considered as a continuous activity in all modes.

Skin wound healing, a dynamic physiological process, progresses through coordinated overlapping phases to restore skin integrity. In some pathological conditions such as diabetes, wounds become chronic and hard-to-heal resulting in substantial morbidity and healthcare costs. Despite much advancement in understanding mechanisms of wound healing, chronic and intractable wounds are still a considerable challenge to nations' health care systems. Extracellular matrix (ECM) components play pivotal roles in all phases of wound healing. Therefore, a better understanding of their roles during wound healing can help improve wound care approaches. The ECM provides a 3D structure and forms the stem cell niche to support stem cell adhesion and survival and to regulate stem cell behavior and fate. Also, this dynamic structure reserves growth factors, regulates their bioavailability and provides biological signals. In various diseases, the composition and stiffness of the ECM is altered, which as a result, disrupts bidirectional cell-ECM interactions and tissue regeneration. Hence, due to the impact of ECM changes on stem cell fate during wound healing and the possibility of exploring new strategies to treat chronic wounds through manipulation of these interactions, in this review, we will discuss the importance/impact of ECM in the regulation of stem cell function and behavior to find ideal wound repair and regeneration strategies. We will also shed light on the necessity of using ECM in future wound therapy and highlight the potential roles of various biomimetic and ECM-based scaffolds as functional ECM preparations to mimic the native stem cell niche.

In this paper, we examine the impact of the macroeconomic determinants of foreign direct investment inflows. We also investigate the moderating role of sanctions in FDI inflows into Iran. The empirical results reveal that macro determinants such as infrastructure, exchange rate, inflation rate, investment return, and governance have a long-run impact on FDI inflows in Iran. Our findings also show that GDP growth rate and trade openness have no significant effect on FDI. Our results indicate that sanctions do not have a significant moderating role in the relationship between macroeconomic factors and foreign direct investment. Surprisingly, international sanctions have a positive relationship with FDI inflows in Iran. Furthermore, sanction has a positive impact on inflation rate and exchange rate in Iran. Finally, our findings show that sanctions have had a significant impact on Iran's economic growth in recent years due to increasing the severity level of sanctions.

Type 1 diabetes (T1D), a spontaneous autoimmune disease, is associated with destruction of insulin-producing β-cells in the pancreas. Since some heat shock proteins (HSP), such as HSP70 exert a protective effect in both tissues and cells, the present study was conducted to elucidate the effects of carbenoxolone (CBX) as an HSP70 inducer on T1D. The disease was induced in male C57BL/6 mice using streptozotocin (STZ) and subjects were allocated to therapeutic 1 and therapeutic 2 groups, as well as negative and positive control groups. The treated mice (therapeutic 1 and therapeutic 2 groups) received 50 mg/kg CBX intraperitoneally every 24 hours, in the therapeutic 1 group the drug was injected before and after disease induction whereas in the therapeutic 2 group the drug was injected only after disease induction. Serum fasting blood sugar (FBS) level, cytokines production (Interferon-gamma (IFN-γ), Interleukin 10 (IL-10), and IL-17), serum HSP70 level and CD4+CD25+Foxp3+ regulatory T cell (Treg) frequency measurements were outperformed 14 days after the last STZ injection. Our results showed that in the treated groups, serum HSP70, IFN-γ, and IL-17 levels were increased in contrast to the untreated groups. The IL-10 level was markedly decreased in comparison to untreated diabetic mice (p0.05). Our results confirm that CBX might through HSP70 induction, followed by increasing IFN-γ level leads to suppression of IL-10 production in diabetic mice resulted in toxic effects on pancreatic islet beta cells and deteriorating of disease.

This study investigates the influence of ownership structure and capital structure on the survival of firms on Iran's stock market from 2005 to 2015. Firm survival is measured in terms of the exit of the firm “i” in year “t” from among 484 firms listed in the Tehran Stock Exchange. We have used a binary logistic regression method to test the hypotheses. The results reveal a significant inverse relationship between capital structure and firm survival and between major ownership and firm survival on the stock market, as well as a significant direct relationship between institutional ownership and firm survival. Thus, firms with a higher ratio of debt to assets have a higher probability of survival. However, those with a higher ratio of institutional ownership are less likely to survive.

Introduction: There are several methods to extract and measure glycogen in animal tissues. Glycogen is extracted with or without homogenization by using cold Perchloric Acid (PCA). Aim: Three procedures were compared to determine glycogen fractions in rat liver at different physiological states. Materials and Methods: The present study was conducted on two groups of rats, one group of five rats were fed standard rodent laboratory food and were marked as controls, and another five rats were starved overnight (15 hour) as cases. The glycogen fractions were extracted and measured by using three methods: classical homogenization, total-glycogenfractionation and homogenization-free protocols. Results: The data of homogenization methods showed that following 15 hour starvation, total glycogen decreased (36.4±1.9 vs. 27.7±2.5, p=0.01) and the change occurred entirely in Acid Soluble Glycogen (ASG) (32.0±1.1 vs. 22.7±2.5, p=0.01), while Acid Insoluble Glycogen (AIG) did not change significantly (4.9±0.9 vs. 4.6±0.3, p=0.7). Similar results were achieved by using the method of total-glycogen-fractionation. Homogenization-free procedure indicated that ASG and AIG fractions compromise about 2/3 and 1/3 of total glycogen and the changes occurred in both ASG (24.4±2.6 vs. 16.7±0.4, p

Introduction: Homogenization of animal tissues with cold Perchloric Acid (PCA) produces two fractions of glycogen, Acid Soluble Glycogen (ASG) and Acid Insoluble Glycogen (AIG). Aim: To determine some physicochemical characteristics of muscle glycogen fractions in two groups of rat. Materials and Methods: An experimental study was conducted on two groups of five male rats. Rats in control group were kept at rest and in case group on 30 minutes physical activity. The content of carbohydrate, protein, phosphate, index and relative Molecular Weights (MWs) were determined for glycogen fractions. Results: Total glycogen decreased following muscular activity (1.40±0.08, mg/g wet muscle vs. 0.97±0.11, p

Summary Background Intra-hepatic metabolism of lipids is subject to hormonal, metabolic and neural regulation, but little is known about the latter. Catecholamines stimulate the output of glucose and inhibit the release of very low density lipoproteins (VLDL) from the liver. Objectives To investigate the effects and involved mechanism of liver denervation on the levels of serum and liver lipids. Methods Two groups of male rats were taken as control and cases and the liver was denerved chemically by 90% phenol in the case group. On the fourth day of the operation, blood samples were taken and the liver homogenized for lipid and glycogen analyses. Cholesterol, triglyceride, HDLc and glucose were measured enzymatically. Total phospholipids were analyzed by the measuring of liberated inorganic phosphate in organic phase. Glycogen was extracted by ethanol and analyzed by phenol/sulphuric acid reagent. In a separate experiment, the rate of triglyceride secretion was measured in vivo by using tyloxapol and compared in two groups. Results The serum concentrations of triglyceride (73.7 ± 6.3 vs. 45.8 ± 1.6 mg/dL, P ≤ 0.003) and cholesterol (87.7 ± 3.7 vs. 67.4 ± 2.2 mg/dL, P ≤ 0.001) were significantly higher in the denerved compared with the control group. The serum glucose showed a significant decrease (170.5 ± 5.4 vs. 140.6 ± 10.7 mg/dL, P ≤ 0.04) in the denerved group while HDLc had no significant difference between the two groups. Denerved rats compared to the control rats had the higher levels of hepatic glycogen (201.1 ± 20.6 vs. 100.7 ± 19.9 mg/g liver, P ≤ 0.02). The contents of liver triglyceride, cholesterol and total phospholipids did not differ significantly between two groups. The mean rate of triglyceride secretion from the liver increased in the denerved group (276.1 ± 16.1 vs. 230.6 ± 7.7 mg/dL.h, P ≤ 0.03). Conclusions Liver denervation increases the levels of serum triglyceride and cholesterol via increases in the rate of VLDL secretion. Liver innervation plays a role on the regulation of metabolism of lipids and carbohydrates.

Introduction: The risk for cardiovascular disease is increased in all stages of the impairment of renal function. It is proposed that serum creatinine is a marker of diabetes and coronary artery disease (CAD) as well as the kidney function. Aim: to study the association of serum creatinine with the likelihood and severity of CAD. The study population consisted of 262 males and 266 females who were classified as CAD cases and controls according to the results of coronary angiography. Results: Patients with CAD compared with the controls had increased levels of serum urea and creatinine. Serum creatinine showed significant positive correlation with male sex, hypertension and negative correlation with total- and HDL-cholesterol and apoAI. Serum urea, uric acid and potassium were the major determinants of creatinine. All hematological parameters were strong negative correlates of creatinine. None of markers of inflammation had significant correlation with creatinine. Creatinine was associated significantly with the prevalence [odds ratio of 1.79 (1.47-2.20), p

1. The vascular endothelium is injured by blood flow abnormalities exacerbated by different risk factors, including markers of haemoconcentration. The aim of the present study was to assess the association between markers of haemoconcentration and dehydration and the prevalence and severity of coronary artery disease (CAD). 2. Subjects in the present study (189 men and 126 women) were classified as either CAD cases or controls according to the results of coronary angiography. The severity of CAD was scored on the basis of the number and the extent of lesions on coronary arteries. Serum electrolytes, osmolality and haematological parameters were measured. 3. Compared with control subjects, patient with CAD had increased levels of serum osmolality, calculated osmolality, tonicity, sodium, glucose and blood urea nitrogen (BUN). Significant differences were also observed in the haematocrit and haemoglobin concentration, but not in erythrocyte counts and total serum protein. On multiple logistic regression analysis adjusting for major risk factors, serum osmolality, glucose and BUN exhibited significant associations with CAD, but the correlations were lessened by diabetes. Analysis using anova showed a significant correlation between serum osmolality, sodium, glucose and BUN and the severity of CAD. The area under the receiver operating characteristic curves, as a relative measure of the test's efficiency, was the highest and significant for serum osmolality, BUN and glucose. 4. The results indicate that some of the markers of dehydration and haemoconcentration are associated significantly with the prevalence and severity of CAD, but the independence of these correlations is questioned. These markers may play a role in the pathogenesis of atherosclerosis.

Introduction: The level of plasma triglyceride is balanced by the rate of secretion into and clearance from the plasma. Tyloxapol (Triton WR1339) is a nonionic detergent that inhibits lipoprotein lipase and hence clearance of triglyceride from the plasma. Aim: To determine the kinetic of plasma lipids and lipoproteins following injection of tyloxapol over a period of two weeks. Materials and Methods: Fifteen male rats were starved overnight and injected intravenously with tyloxapol (400mg/kg). Blood samples were taken in three steps as, the early (1-6 hours), the middle (1-2 days) and the third (3-9 days) phase. Plasma total cholesterol and triglyceride were measured by enzymatic methods and total phospholipids were analysed as molybdenum blue. Serum lipoproteins were fractionated by electrophoresis on agarose gel (Sebia Inc). Results: The changes of plasma lipids following tyloxapol injection showed three distinctive phases. The early phase lasts at least 6 hours, and the concentrations of triglyceride, total cholesterol and phospholipids increased linearly. The rate of triglyceride secretion was 259.7 + 8.1 mg/h.dl in this phase, which was comparable to the mean rate of 250.6 + 37.0 mg/h.dl or 102.8 + 15.2 mg/h.kg body in starved male rat. During the next 48 hour the lipids continued to accumulate but at a lower rate, and the levels of triglyceride, cholesterol and total phospholipids rose up to about 3200, 586 and 715 mg/dl respectively. In the last phase, the levels of plasma lipids decreased toward the basal levels after 5 days. In serum lipoprotein electrophoresis, the VLDL and LDL increased and HDL fraction disappeared simultaneously during the initial 2 hours of tyloxapol injection. The VLDL fell down toward the normal range, preceded to the reappearance of HDL during 5 days. Conclusion: A single intravenous injection of tyloxapol shows three distinctive phases. In the early phase, triglyceride accumulates linearly and the rate of its increment in plasma is a good estimate of the rate of VLDL secretion from the liver.

The terms osmotic pressure, osmotic coefficient, osmole, osmolarity, osmolality, effective osmolality and delta osmolality are formally defined. Osmole is unit of the amount of substance, one mole of nonionized impermeant solute is one osmole. Assuming an ideal solution, osmotic pressure (π) in mmHg is 19.3 times the osmolarity. Osmolarity is defined as the number of milliosmoles of the solutes per liter of solution. Suitable equations are presented for the rapid calculation of the osmolarity of different solutions. The concentrations of electrolytes are expressed by mEq/L that is, equal to their osmolarity as mOsm/L. If the solute concentration (C) is expressed as mg/L, mg/dL and g%, osmolarity is calculated as: C.n' /MW, C.n' (10)/MW and C.n' (10(4))/MW respectively. Osmolality is milliosmoles of solutes per one kilogram (or liter) of water of solution (plasma) and is calculated by osmolarity divided to plasma water. The osmolal concentration is corrected to osmolal activity by using the osmotic coefficient, φ. The salts of sodium (choloride and bicarbonate) and nonelectrolyte glucose and urea are the major five osmoles of plasma. The equation: Posm =2 [Na(+)]+glucose (mg/dL)/18+BUN (mg/dL)//2.8 is also the simplest and best formula to calculate plasma osmolality. The concentration of only effective osmoles evaluates effective osmolality or tonicity as: Eosm =2 [Na(+)]+glucose/18. The normal range of plasma tonicity is 275-295mOsm/kg of water. The difference between the measured and calculated osmolality is called osmolal gap. It is recommended to withdraw the formula of Dorwart-Chalmers from the textbooks and autoanalyzers and to use the simplest equation of Worthley et al. as the best equation for calculating serum osmolality. Furthermore the normal ranges of osmolal gap also must be corrected to 0±2mOsm/L.

This empirical study explores first the relationship between operating years and entry strategies based on wholly-owned and joint venture companies. Second, we examine the effects of equity ownership, size, entry strategy and subsidiary age on the sales growth ratio and the subsidiary's survival. Our findings show that in recent periods, the multi-national companies (MNCs) prefer to acquire high levels of equity ownership, including full ownership subsidiaries, especially when the subsidiary is in the manufacturing industry. Our results imply that capital, the age of the venture, the number of employees and full equity ownership affect survival. Finally, we find that subsidiaries with a small number of employees are likely to have a superior sales growth ratio and are more likely to survive.

This empirical study explores first the relationship between operating years and entry strategies based on wholly-owned and joint venture companies. Second, we examine the effects of equity ownership, size, entry strategy and subsidiary age on the sales growth ratio and the subsidiary's survival. Our findings show that in recent periods, the multi-national companies (MNCs) prefer to acquire high levels of equity ownership, including full ownership subsidiaries, especially when the subsidiary is in the manufacturing industry. Our results imply that capital, the age of the venture, the number of employees and full equity ownership affect survival. Finally, we find that subsidiaries with a small number of employees are likely to have a superior sales growth ratio and are more likely to survive.

Background The hypothesis is proposed that the atherogenicity of lipoporotein fractions is correlated with the content of unesterified cholesterol. Objectives To evaluate the role and prognostic values of unesterified and esterified cholesterol in lipoprotein fractions for coronary artery disease (CAD). Design and methods The study population consisted of 400 patients who were divided to CAD controls and cases according to the data of coronary angiography. Fractional cholesterol esterification (FCE) as well as the complete profile of lipids and (apo)lipoproteins were determined. Results Total cholesterol was increased significantly in CAD patients (196.3 ± 52.3 mg/dL vs. 185.7 ± 48.0, p≤ 0.049) and the increment occurred totally in unesterified portion (77.2 ± 28.4 mg/dL vs. 71.1 ± 24.4, p≤ 0.031). HDL cholesterol showed a significant decrease in CAD group (39.9 ± 9.5 mg/dL vs. 44.6 ± 10.5, p≤ 0.001), but the decrement occurred wholly in the esterified portion (26.2 ± 9.2 mg/dL vs. 31.1 ± 8.1, p≤ 0.001). NonHDL cholesterol was increased significantly in CAD group (156.8 ± 48.3 mg/dL vs. 140.3 ± 43.6, p≤ 0.001), and the changes occurred in both un- and esterified portions. FCE in HDL was diminished significantly in CAD patients (64.8 ± 13.9% vs. 69.3 ± 7.9, p≤ 0.01). In multivariate logistic regression analysis, unesterified cholesterol in NonHDL (UeNonHDLc) and esterified cholesterol in HDL (EsHDLc) excluded total cholesterol and HDLc respectively from the regression equation. In ROC analysis, the ratio of UeNonHDLc/EsHDLc was the strongest predictor for CAD among cholesterol subfractions. Conclusions The results confirm that UeNonHDLc is atherogenic and EsHDLc is antiatherogenic and are independent risk factors for CAD.

Excretory–secretory antigens (ESAs) of Toxoplasma gondii are one of the candidates for immunization against toxoplasmosis. For evaluation of immunization, we determined the kinetics of the distribution of Toxoplasma and parasite load in different tissues of mice immunized by ESAs. In this experimental study, 36 mice in case (n = 18) and control (n = 18) groups were immunized with ESAs and PBS, respectively. After 2 weeks, mice were challenged intraperitoneally with Toxoplasma virulent RH strain. Blood and different tissues (brain, spleen, liver, heart, kidney, and muscle) were collected daily after challenge (1, 2, 3 and last day before death). Parasite load was calculated using Real time QPCR targeted at the B1 gene. ESAs as vaccine in different tissues showed various effects. However, infected mice which received the vaccine in comparison with control group, displayed a drastically decreasing in parasite burden, in their blood and tissues (P = 0.000). These results indicated that ESAs with reduction of parasite load in different tissues of host could be evaluable candidate for the development of immunization strategies against toxoplasmosis.

Background Low-density lipoprotein cholesterol (LDLc) can be calculated or measured directly and their accordance is the subject of controversy. Objectives The aim of this study was to identify the independent predictors of LDLc, to formulate the best equation for calculating LDLc and to evaluate the validity of it and the published formulas, including the new method with adjustable coefficient. Methods The profile of serum lipids and (apo)lipoproteins of 310 subjects was used to determine the most accurate formula for calculating serum LDLc. Serum lipids, lipoproteins and apolipoproteins were measured by enzymatic, new homogenous and immunoturbidometric methods, respectively. Results Multiple linear regression analysis indicates that total cholesterol, apoB, HDLc and triglyceride are independent predictors of LDLc. We proposed four new formulas to calculate LDLc. As total cholesterol (TC) is the major determinant of LDLc, it can be estimated simply as 0.545 of total cholesterol. Inclusion of HDLc, triglyceride, apoB and a constant value improved the equation slightly. The equation of: LDLc (mg/dl) = 0.75 TC − 0.5 HDLc − 0.1 TG had the lowest mean and SD of difference among all the methods examined here. LDLc was also calculated by the new modified Friedewald's equation using adjustable factor from Martin's table, but it did not improve the results significantly. LDLc gap was correlated significantly and positively with triglyceride and negatively with cholesterol or its subfractions. Conclusions Our data suggest the simplest formula: LDLc = 0.545 TC or a more detailed: LDLc = 0.75 TC − 0.5 HDLc − 0.1 TG be used for calculating serum LDLc.

The presence of elevated circulating triacylglycerol (TG)-rich very low density lipoprotein (VLDL) and apolipoprotein B-100 (apoB-100) levels represents an independent risk factor for coronary artery disease. Triacylglycerol hydrolase catalyzes the mobilization of cytoplasmic TG stores. To test the hypothesis that the enzyme plays a role in the provision of core lipids for the assembly of VLDL, we inhibited the lipase activity in primary rat hepatocytes and analyzed lipid and apoB synthesis and secretion. Inhibition of lipolysis resulted in a dramatic decrease in secretion of TGs. In addition, secretion of cholesteryl ester and phosphatidylcholine was substantially decreased. Analysis of secreted apolipoproteins indicated that apoB-100 secretion was much more sensitive to lipase inhibition than was apoB-48 secretion, perhaps because of the ability of apoB-48 to be secreted as a relatively lipid-poor particle. The results agreed with those obtained with hepatoma cells transfected with triacylglycerol hydrolase cDNA, in which preferential lipidation of apoB-100 was observed. Together, our findings provide evidence that inhibition of intracellular TG hydrolysis significantly decreases apoB-100 secretion and suggest that triacylglycerol hydrolase may be a suitable pharmacological target in efforts to lower plasma lipid levels.

This empirical study explores the impact of knowledge development factors, parent firm-specific and subsidiary characteristics on foreign affiliated performance. First, we examine the ownership and performance (based on return on asset, return on sales and profitability) of foreign affiliated in Japan. Second, we extend the subsidiary’s factors with parent company’s firm factors in order to analyze the performance and ownership advantages based on wholly owned subsidiary (WOS) and international joint venture (IJV). Third, we explore the relationship between firm factors and foreign ownership ratio.Our finding suggested that first, when a subsidiary operates in the manufacturing industry; MNCs prefer to have a majority of equity ownership.Second, the factors of industry, foreign employees and size of parent firm and subsidiary, demonstrate a statistically significant on performance. Finally, our findings indicate that foreign ownership ratio has a positive relationship with knowledge transfer factors, import and export ratio of foreign affiliates.

This empirical study explores first the relationship between type of industry and subsidiary age, export ratio and MNCs’ firm factors. Second, we examined the impact of country of origin, foreign ownership and parent’s specific factors on asset growth ratio (AGR). Based on data derived from 2500 foreign companies in Japan, the findings show that the factors of foreign ownership, experience in host market, country of origin, export and parents company’s sales and the number of employees as a proxy of firm size have significantly effect on AGR. Also our finding shows that foreign companies in manufacturing industries are more likely to be as an international joint venture with a foreign manager and higher ratio of import and greater number of foreign employees. Finally, contrary to our expectations, we found that the total asset of parent company has negatively associated with type of industry. In the other word, firms in service industries are more likely to have greater total asset than those in manufacturing sectors.

It has been shown that microalbuminuria is an independent risk factor for cardiovascular diseases in diabetics, hypertensive patients and in the general population. However, few data has addressed the correlation of microalbuminuria with the severity of coronary artery disease (CAD). The aim of the study was to assess the association of microalbuminuria with the prevalence and severity of CAD.The subjects, 79 men and 74 women aged 45-70 years, were classified as CAD-negative and CAD-positive according to the results of coronary angiography. The severity of CAD was scored on the basis of the number and the extent of lesions within the coronary arteries. Urine albumin excretion was measured in 24 h urine samples by method of nephelometry.Coronary artery disease occurred more frequently in males than in females and in smokers than in non-smokers. There were no significant differences in the prevalence of hypertension and hypercholesterolemia between two groups. Microalbuminuria was more prevalent in CAD-positive patients than in controls (62.9% vs. 8.8%; por = 0.001). Patients with microalbuminuria compared with the controls had increased prevalence of one (15.3% vs. 7.4%, p pound 0.001), two (50% vs. 22.2%, por = 0.001), and three vessel disease (29.2% vs. 19.8%, por = 0.001). Microalbuminuria exhibited a significant correlation with the severity of CAD (r = 0.40; por = 0.001).Patients with microalbuminuria have more severe angiographically detected CAD than those without microalbuminuria. The results indicate that microalbuminuria exhibits a significant association with the presence and severity of CAD.

Background Synergistic interactions between elevated serum lipoprotein(a) [Lp(a)] and other unfavorable risk factors have been proposed to cause very high risk for coronary artery disease (CAD). The aim of this study was to examine the potential interactions between Lp(a) and other risk factors. Methods The profiles of serum (apo)(lipo)proteins, markers of inflammation, indicators of hemoconcentration as well as classical risk factors were determined in 264 clinically stable angiographically documented subjects. Correlation, linear and logistic regression and stratification analyses were performed. Results The frequency and severity of CAD and the prevalence of diabetes mellitus were significantly higher in the 3rd relative to 1st tertile of Lp(a). Subjects with Lp(a) levels in the upper tertile had significantly higher levels of serum glucose, total cholesterol and low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (apoB), calcium, phosphate and their ion product. Bivariate correlation analysis indicated that serum Lp(a) was associated positively with the occurrence and severity of CAD, diabetes mellitus and the levels of serum glucose, cholesterol, LDL-C, apoB, calcium, phosphate and inversely to physical inactivity. In linear regression analysis, LDL-C (or apoB), diabetes, physical inactivity and phosphate were the major independent determinants of Lp(a) values. In multiple logistic regression analysis, after adjusting for major risk factors, Lp(a) showed a significant and independent association with the prevalence of CAD. By constructing dummy combined variables, elevated Lp(a) accompanied with diabetes or high levels of serum glucose, apoB and cholesterol exhibited an amplified high risk for CAD. Conclusions The results indicate that serum Lp(a) does interact multiplicatively with diabetes, apoB and cholesterol. The simultaneous assessment of Lp(a) and interactive risk factors enhances the discriminating value for CAD.

Background: It is hypothesized that the impacts of life events accumulate and can trigger and promote atherosclerosis in susceptible individuals. In the current study, the correlation of total life stressors during 1 year was investigated relative to coronary artery disease (CAD). Methods: The study population consisted of 148 males and 152 females aged 35-76 years. The subjects were classified as CAD cases and controls according to the results of coronary angiography. The severity of CAD was scored on the basis of the number and the extent of lesions at coronary arteries. The stressful events of life were assessed using Holmes-Rahe Questionnaire and was presented as total psychological stress scores per year (TPSS). Results: The frequency of cigarette smoking, diabetes mellitus, and hypertension was more prevalent in CAD cases than control subjects. The levels of TPSS were increased in patients with CAD compared to the controls (160.3 ± 71.3 vs. 139.8 ± 66.5, P = 0.020). TPSS was also associated positively with the levels of uric acid, erythrocytes counts, erythrocyte sedimentation rate, aspirin consumption, and negatively with high-density lipoprotein-cholesterol and apo-AI. In logistic regression analysis, TPSS correlated with the occurrence of CAD by the odds ratio of 1.773 (1.073-2.930), P = 0.025, but the association was weakened after adjustment for classical risk factors, especially hypertension. TPSS exhibited significant association with the severity of CAD [F (3,274) = 2.6, P = 0.051]. Conclusions: The results suggest that TPSS are associated with the occurrence and severity of CAD significantly, but the association is not independent.

BACKGROUND The ratio of low- to high-density lipoprotein-cholesterol (LDL-C/HDL-C) conventionally represents the balance of proatherogenic and anti-atherogenic lipids. However, growing evidence supports the idea that the ratio of apolipoprotein (apo) B/apoAI is a better index for risk assessment of coronary artery disease (CAD). The aim of this study was to evaluate the efficiency of advanced profile of serum (apo)lipoproteins for predicting stable CAD in secondary prevention. METHODS The study subjects, 138 men and 126 women aged 40-70 years, were classified as CAD cases or controls, according to the results of coronary angiography. The severity of CAD was scored on the basis of the number and extent of lesions in coronary arteries. Serum (apo)lipoproteins were measured by immunoturbidometric and electrophoresis methods. RESULTS Patients with CAD compared with controls had increased serum levels of triglycerides (2.6+/-2.0 vs. 2.0+/-1.2 mmol/L, p< or =0.005), apoB (1.36+/-0.31 vs. 1.19+/-0.24 g/L, p< or =0.0001), lipoprotein(a) [Lp(a)] (0.69+/-0.60 vs. 0.43+/-0.31 g/L, p< or =0.0001) and apoB/apoAI ratio (1.07+/-0.32 vs. 0.87+/-0.18, p< or =0.0001), and decreased serum levels of HDL-C (1.02+/-0.29 vs. 1.11+/-0.34 mmol/L, p< or =0.03), apoAI (1.32+/-0.22 vs. 1.37+/-0.19 g/L, p< or =0.04) and LDL-C/apoB ratio (0.91+/-0.32 vs. 1.02+/-0.25 mmol/g, p< or =0.01). Multiple logistic regression analysis after adjusting for major risk factors showed that the apoB/apoAI ratio, apoB and Lp(a) were among seven significant and independent determinants of CAD. The area under the receiver operating characteristic (ROC) curves (AUC) as a relative measure of test efficiency was highest and significant for the apoB/apoAI ratio (AUC=0.71, p< or =0.0001), apoB (0.67, p< or =0.0001), Lp(a) (0.63, p< or =0.001), the LDL-C/apoB ratio (0.62, p< or =0.006), triglycerides (0.62, p< or =0.004) and apoAI (0.58, p< or =0.05). ANOVA analysis showed significant association for the apoB/apoAI ratio, apoB, Lp(a) and triglycerides, and moderate association for total cholesterol and its subfractions, with the severity of CAD. CONCLUSIONS The results indicate that the apoB/apoAI ratio, apoB and Lp(a) are independent risk factors for CAD and are superior to any of the cholesterol ratios. We suggest using the apoB/apoAI ratio as the best marker of CAD in clinical practice.

Background The role and diagnostic value of markers of inflammation is well recognized in acute coronary syndromes but it is uncertain in patients with stable coronary artery disease (CAD). This study was done to investigate the association of markers of inflammation with the occurrence and severity of CAD and to evaluate their predictive values. Methods Markers of inflammation, electrophoresis serum protein fractions, serum (apo)lipoproteins and classical risk factors were determined in 270 angiographically documented subjects. The subjects were classified as CAD cases and controls according to angiography. The severity of CAD was scored on the basis of the number and extent of lesions. Results The counts of total leukocytes (7.14 ± 1.86 cell/nl vs. 6.58 ± 1.62, p ≤ 0.02), neutrophils (3.95 ± 1.42 vs. 3.59 ± 1.07, p ≤ 0.05) and eosinophils (0.25 ± 0.28 vs. 0.19 ± 0.24, p ≤ 0.03) were increased significantly, whereas the concentrations of high-sensitivity C-reactive protein (hsCRP, 2.03 (0.0−32.0) mg/l vs.1.72 (0.09−11.36), p ≤ 0.07) changed modestly in CAD patients relative to controls. There were no significant differences in the counts of monocytes and lymphocytes and the concentrations of erythrocyte sedimentation rate (ESR) and any five fractions of serum proteins between two groups. The counts of total leukocytes, neutrophils and eosinophils, but not hsCRP and ESR exhibited significant associations with the severity of CAD. In univariate logistic regression analysis, leukocytes count associated significantly (OR = 1.97, p ≤ 0.01) whereas hsCRP modestly (OR = 1.76, p ≤ 0.06) with the occurrence of CAD. The association was lessened by diabetes mellitus in multivariable adjustment. Receiver operating characteristic (ROC) analysis showed that, only total leukocyte and differential counts had significant potency to predict CAD (area under curve, AUC = 0.60 ± 0.04, p ≤ 0.02). Conclusions The total leukocytes count and its subgroups are associated with the presence and severity of CAD, but the associations were not independent. The efficiency was questioned for hsCRP, ESR and five fractioned serum proteins to identify stable CAD.

Background: Plasma high-sensitivity CRP (hsCRP) is a marker of inflammation, and it is reported to link with coronary artery disease (CAD). Interactions between elevated serum hsCRP and other unfavorable risk factors have been proposed to cause high risk for CAD. Objectives: To examine the potential interactions between serum hsCRP and lipids and non-lipidic risk factors. Methods: Markers of inflammation, the profiles of serum (apo)(lipo) proteins as well as classical risk factors were determined in 270 clinically stable angiographically documented subjects. The patients were stratified into tertiles according to hsCRP distribution. Results: The Framingham CAD scores, relative and absolute risk for CAD and the prevalence of diabetes mellitus and hypertension were significantly higher in 3rd relative to 1st tertile of hsCRP. Subjects with hsCRP levels in the upper tertile had significant higher levels of serum glucose, triglyceride, apolipoprotein (apo)B, apoB/apoAI ratio and the counts of total leukocyte and neutrophil and lower levels of HDL-C, albumin and the ratio of albumin/globulins. Analyses by bivariate correlation as well as linear regression showed that serum hsCRP was associated positively with the occurrence of diabetes and hypertension, the counts of total leukocyte and neutrophil and the levels of serum glucose, uric acid, apoB, apoB/apoAI ratio, α1- and α2-globulins and inversely with albumin, albumin/globulin ratio and HDL-C. By constructing dummy combined variables, elevated hsCRP accompanied with male sex, diabetes, hypertension and high levels of serum glucose, apoB, apoB/apoAI ratio and cholesterol exhibited amplified high risk for CAD. Conclusions: The results show that hsCRP does interact multiplicatively with apoB and some variables of metabolic syndrome. The simultaneous assessment of hsCRP and interactive risk factors enhances discriminating value for CAD. It is suggested to use hsCRP in conjunction with apoB or apoB/apoAI ratio instead of cholesterol ratios in global risk assessment.

The associations of serum calcium and phosphorus concentrations as well as other cardiovascular risk factors were investigated in relation to the existence and severity of coronary heart disease (CHD) in 260 clinically stable, angiographically defined CHD patients aged 40-70 years. The subjects were classified as CHD(+) cases if one or more coronary arteries had a significant stenosis (> or =70%) and CHD(-) controls if there was no stenosis (< or =10%) in any artery. The severity of coronary occlusion was scored on the basis of the number and extent of lesions, as normal, mild, moderate or severe. Fasting serum concentrations of electrolytes, lipids and (apo)lipoproteins were determined. The concentrations of serum total calcium (2.41 +/-0.14 vs. 2.33 +/- 0.22 mmol/L, p < or = 0.05), albumin-corrected calcium (2.33 +/- 0.25 vs. 2.23 +/- 0.25 mmol/L, p < or = 0.01), phosphorus (1.32 +/-0.21 vs. 1.25 +/- 0.17 mmol/L, p < or = 0.007) and the ion product of calcium and phosphorus (3.16 +/- 0.58 vs. 2.91 +/- 0.50, p < or =0.0001) were significantly higher in the CHD(+) compared to the CHD(-) group. Patients with CHD compared with controls had increased serum levels of triglyceride, total cholesterol, low-density lipoprotein-cholesterol (LDL-C), apolipoprotein B (apoB), lipoprotein(a) [Lp(a)] and decreased serum levels of high-density lipoprotein (HDL)-C and apoAI. Multiple logistic regression analysis showed strong and significant association between diabetes mellitus (odds ratio, OR = 5.24, p < or = 0.0001), male gender (OR = 8.84, p < or =0.0001), Lp(a) (OR = 1.014, p < or =0.006), hypertension (OR = 2.61, p < or =0.02), apoB (OR = 1.031, p < or =0.001), age (OR = 1.055, p < or =0.003), phosphorus (OR = 2.438, p < or =0.01), albumin-adjusted calcium (OR = 1.532, p < or =0.05), cholesterol (OR = 1.009, p < or =0.05) and the occurrence of CHD. On the basis of bivariate correlation analysis, serum-adjusted calcium was positively correlated with the levels of cholesterol (r = 0.285, p < or =0.0001), LDL-C (r = 0.320, p < or =0.0001), Lp(a) (r = 0.173, p < or = 0.005), apoB (r = 0.237, p < or =0.0001), LDL-C/apoB ratio (r = 0.180, p < or= 0.007), apoAI (r = 0.181, p < or =0.003) and inversely to HDL-C (r = -0.146, p < or =0.02) and HDL-C/apoAI ratio (r = -0.263, p < or =0.0001). Serum phosphorus concentration was a significant correlate of triglyceride (r = 0.199, p < or =0.001) and Lp(a) (r = 0.129, p < or =0.04). The results demonstrated that serum calcium and phosphorus are associated with the prevalence and severity of CHD, probably through correlation with atherogenic lipids and (apo)lipoproteins. Serum calcium and phosphorus and their ion product were also independent risk factors for CHD.

The electrophoretic pattern of serum proteins of 85 patients carrying different types of neoplasia and 85 matched healthy adults were comparatively studied by agarose gel electrophoresis, to find out if there is a specific protein pattern common to different types of cancer. Each protein fraction was analyzed quantitatively by densitometry. Multivariate logistic regression and receiver operating characteristic (ROC) analyses were performed using SPSS software. When total protein and albumin were measured by colorimetric methods, cancer patients, compared to controls, had a decreased concentration of total protein (66.0+/-11.5 g/L vs. 76.4+/-6.8 g/L, p< or =0.0001) and of albumin (39.0+/-8.1 g/L vs. 46.0+/-4.3 g/L, p< or =0.0001). The electrophoretic data of serum proteins showed that the ratio of albumin to globulin (0.92+/-0.30 vs. 1.21+/-0.16, p< or =0.0001), percent of the fractions albumin (46.7+/-8.5% vs. 54.4+/-3.5%, p< or =0.0001) and beta-globulin (11.6+/-4.4% vs. 13.0+/-1.9%, p< or =0.001) were decreased and alpha(1)- (5.3+/-2.5% vs. 2.9+/-0.8%, p< or =0.0001), alpha(2)- (13.5+/-4.8% vs. 11.3+/-2.1%, p< or =0.0001) and gamma-globulins (23.0+/-7.7% vs. 18.3+/-3.1%, p< or =0.0001) were significantly increased in cancer patients relative to controls. Cancer patients also had higher counts of leukocytes (7.98+/-3.11, x10(9) cells/L vs. 6.33+/-1.68 x10(9) cells/L, p< or =0.0001) and erythrocyte sedimentation rate (35.9+/-23.5 mm/h vs. 14.1+/-9.5 mm/h,p< / =0.0001). On the basis of univariate analysis, a protein profile out of the normal ranges was more prevalent in cancer patients than in controls. Analysis of the data using multiple logistic regression indicated that the prevalence of cancer was strongly associated with the serum proteins' profile, and alpha(1)-globulin, erythrocyte sedimentation rate, total protein and the ratio of albumin to globulin were the best parameters to discriminate between malignant and healthy states. The area under the ROC curves were the same for most components of the serum proteins' profile at about 0.75+/-0.09, p< or =0.001. We conclude that the profile of serum proteins indicates high diagnostic values for discriminating between cancer patients and healthy individuals and may be useful as an adjunct diagnosis for detection of malignancy.

BACKGROUND There are several methods for calculating serum osmolality, and their accordance with measured osmolality is the subject of controversy. METHODS The concentrations of sodium, potassium, glucose, blood urea nitrogen (BUN) and osmolalities of 210 serum samples were measured. Two empirical equations were deduced for the calculation of serum osmolality by regression analysis of the data. To choose the best equation, chemical concentrations were also used to calculate osmolalities according to our formulas and 16 different equations were taken from the literature and compared with the measured osmolalities. Correlation and linear regression analyses were performed using Excel and SPSS software. RESULTS Multiple linear regression analysis showed that serum concentrations of sodium (beta = 0.778, p< or = 0.000), BUN (beta = 0.315, p < or = 0.000), glucose (beta = 0.0.089, p < or = 0.007) and potassium (beta = 0.109, p < or = 0.008) are strong predictors of serum osmolality. The data were also analyzed by manual linear regression to yield the equations: osmolality = 1.897[Na + ]+glucose+BUN+13.5, and osmolality = 1.90[Na+ + K+]+glucose+BUN+5.0. The osmotic coefficient for sodium and potassium solutes was deduced to be 0.949 from the slope of the curves of measured osmolality vs. [Na+] and [Na+ + K+], respectively. The inclusion of a BUN value in the equation for osmolality increased the correlation coefficient by approximately 450% and decreased the SD of difference by approximately 35% (p < or = 0.002). Inclusion of the osmotic coefficient for sodium solutes caused an underestimation of measured osmolality and positive osmolal gap unless an appropriate coefficient, constant value and/or the potassium value were included in the equation. The agreement was not improved when molal chemical concentrations were used instead of molar values. The formula presented by Dorwart and Chalmers gave inferior results to those obtained with our formulas. CONCLUSIONS Our data suggest use of the Worthley et al. formula Osm = 2[Na +]+glucose+BUN for rapid mental calculation and the formulas of Bhagat et al. or ours for calculation of serum osmolality by equipment linked to a computer.

The effects of a calmodulin antagonist W-7 were studied on the synthesis and secretion of lipids in primary rat hepatocytes and McArdle-RH7777 cells. In time course experiments, W-7 (20 microM) inhibited secretion of newly synthesized triacyl[(3)H]glycerol by 35%. When the cells were pre-treated overnight with W-7 (20 microM), followed by incubation with [(3)H]oleate, a significant decrease in the secretion of triacylglycerol (TG) and cholesteryl ester (CE) was observed. De novo synthesis of cholesterol from acetate or mevalonolactone was inhibited by W-7, but not glycerolipid synthesis from glycerol and oleic acid precursors. Concentration-response curves for the effects of overnight pre-incubation with W-7 followed labeling with [(3)H]glycerol and [(14)C]mevalonolactone revealed that: (1). the inhibitory effect of W-7 was concentration-dependent and appeared even at the lowest concentration examined (1 microM). W-7 at a concentration of 20 microM suppressed secretion of TG by 60% (Por=0.002), phosphatidylcholine (PC) by 31% (Por=0.05), CE by 59% (Por=0.002) and cholesterol by 64% (Por=0.002). (2). The incorporation of [(14)C]mevalonolactone into cellular cholesterol and CE was decreased significantly, while W-7 did not have any significant effect upon incorporation of [(3)H]glycerol into glycerolipids, except at the highest concentration examined (50 microM), where synthesis of both TG and PC was significantly suppressed. (3). While the percentage of secreted de novo synthesized glycerolipids and CE decreased proportionally with increasing concentration of W-7, the percentage of secreted newly made cholesterol remained unaffected at any concentration of W-7. In the absence of W-7, about 19% of newly formed cholesterol became esterified into CE, whereas W-7 increased cholesterol esterification in a concentration-dependent manner. (4) W-7 (20 microM) also suppressed the secretion of preformed cholesterol by 24% and CE by 55% but did not affect the recruitment of preformed cholesterol for esterification. About 6.5% of pre-labeled cholesterol and 20% of CE were directed to secretion, which was suppressed in the presence of W-7 by 17% (Por=0.09) and 48% (Por=0.001), respectively. These results suggest that, W-7 in the range of 1-20 microM inhibited de novo synthesis of cholesterol and the secretion of both de novo synthesized and preformed lipids.