Low Molecular Weight Substances Research Articles

Effects of Ginsenoside Rg<sub>3</sub> on α9α10 Nicotinic Acetylcholine Receptor-Mediated Ion Currents

Ginsenosides is a low molecular weight substance found in ginseng as one of the active ingredients. Ginsenosides, like other herbal medicines, has a wide range of neuropharmacological actions including neuroprotective effects. The α9α10 nicotinic acetylcholine receptor is one of numerous nicotinic acetylcholine receptors that exists as a heteropentameric form in auditory hair cells of the cochlea. In this study, we report the effects of ginsenosides on rat α9α10 nicotinic acetylcholine receptor-mediated ion currents using the two-electrode voltage clamp technique. Treatment with acetylcholine evoked inward currents (IACh) in oocytes heterologously expressing the α9α10 nicotinic acetylcholine receptor. Ginsenosides blocked IACh in order of potency of Rg3> Rb2> CK>Re = Rg2> Rf>Rc> Rb1> Rg1 with reversible manners, and the blocking effect of Rg3 on IACh was same after pre-application than co-application of Rg3. The half maximal inhibitory concentration (IC50) of Rg3 was 39.6 ± 4.9 µm. Rg3-induced IACh inhibition was not affected by acetylcholine concentration and was independent of membrane holding potential. Although the inhibitory effect of Rg3 on IACh was abolished in oocytes expressing α9 subunit alone, indicating that the presence of α10 subunit might be required for Rg3-induced regulations of α9α10 nicotinic acetylcholine receptor channel activity. These results indicate that α10 subunit of α9α10 nicotinic acetylcholine receptor might play an important role in Rg3-induced regulation of the α9α10 nicotinic acetylcholine receptor.

Renal markers in normal and hypertensive disorders of pregnancy in Indian women: a pilot study

BackgroundAltered renal function is an essential component of the pathophysiological process in pre-eclampsia. Kidneys play an important role in the turnover of low molecular weight substances such as creatinine, uric acid and cystatin C. The present study was undertaken if these serum markers were characteristically altered in Indian pregnant women.MethodsSerum levels were therefore determined in samples from 69 healthy women at term as well as in 27 samples of patients with Pregnancy induced hypertension (PIH) and in 20 patients with pre-eclampsia (PE).ResultsThe levels of all three components were significantly higher in pre-eclamptic patients when compared to healthy controls with the mean ± SD being 1.47 ± 0.9 vs. 1.06 ± 0.2 for cystatin C, 0.95 ± 0.2 vs. 0.67 ± 0.1 for creatinine and 6.13 ± 1.8 vs. 4.28 ±1.1 for uric acid respectively. In PIH cystatin C was significantly higher, 1.25 ± 0.9 unlike creatinine, 0.67 ± 0.14 and uric acid, 4.30 ± 1.0. Receiver operating characteristic (ROC) plots demonstrated that the diagnostic accuracy of serum creatinine was superior to serum uric acid and serum cystatin C and serum uric acid was better than serum cystatin C.ConclusionThe maternal serum cystatin C, creatinine and uric acid were all significantly elevated at the end of pregnancy in pre-eclampsia compared to those of healthy pregnant women. If this rise in the above markers during early pregnancy could predict the onset of PIH/PE, needs to be investigated.

Peptide Derived from HIV-1 TAT Protein Destabilizes a Monolayer of Endothelial Cells in an in Vitro Model of the Blood-Brain Barrier and Allows Permeation of High Molecular Weight Proteins

Most chemotherapeutic agents are blood-brain barrier (BBB) impermeants. HIV-1-derived TAT protein variants contain a transmembrane domain, which may enable them to cross the BBB and reach the brain. Here we synthesized CAYGRKKRRQRRR, a peptide containing a cysteine moiety attached to the N terminus of the transmembrane domain (C-TAT peptide), and studied its effects in an in vitro BBB model, which we found to reflect penetration by a receptor-independent pathway. Incubation of the brain capillary endothelial cell monolayer with 0.3-0.6 μmol/ml of this C-TAT peptide, for a period of 1-2 h, destabilizes brain capillary endothelial cell monolayer and introduces the ability of impermeant therapeutic agents including high molecular weight proteins to penetrate it substantially. The cysteinyl moiety at position 1 of the C-TAT peptide contributes largely to the destabilizing potency and the penetration efficacy of impermeant substances. The destabilizing effect was reversed using heparin. In summary, experimental conditions allowing a significant increase in entry of impermeant low and high molecular weight substances from the luminal (blood) to the abluminal side (brain) were found in an in vitro BBB model reflecting in vivo protein penetrability by a receptor-independent pathway.

Effect of thermal treatment on the chemical characteristics of wood from Eucalyptus grandis W. Hill ex Maiden under different atmospheric conditions

Thermal treatment (thermal rectification) is a process in which technological properties of wood are modified using thermal energy, the result of which is often value-added wood. Thermally treated wood takes on similar color shades to tropical woods and offers considerable resistance to destructive microorganisms and climate action, in addition to having high dimensional stability and low hygroscopicity. Wood samples of Eucalyptus grandis were subjected to various thermal treatments, as performed in presence (140ºC; 160ºC; 180ºC) or in absence of oxygen (160ºC; 180ºC; 200ºC) inside a thermal treatment chamber, and then studied as to their chemical characteristics. Increasing the maximum treatment temperatures led to a reduction in the holocellulose content of samples as a result of the degradation and volatilization of hemicelluloses, also leading to an increase in the relative lignin content. Except for glucose, all monosaccharide levels were found to decrease in samples after the thermal treatment at a maximum temperature of 200ºC. The thermal treatment above 160ºC led to increased levels of total extractives in the wood samples, probably ascribed to the emergence of low molecular weight substances as a result of thermal degradation. Overall, it was not possible to clearly determine the effect of presence or absence of oxygen in the air during thermal treatment on the chemical characteristics of the relevant wood samples.

Removal of different fractions of NOM foulants during demineralized water backwashing

The effectiveness of demineralized water backwashing on fouling by different fractions of NOM was investigated in this study. Two types of natural surface water (Schie canal and Biesbosch reservoir) were tested to confirm the improvement of demineralized water backwashing on fouling control, and LC-OCD analysis was conducted on Schie canal water to find out which fraction of NOM was removed with those backwashes. Results derived from natural waters showed that demineralized water backwashing substantially improved UF fouling control. LC-OCD analyses showed both UF permeate and demineralized water backwashes were effective on removing part of biopolymers, but demineralized water is also effective for humic substances and a limited amount of low molecular weight substances. However, based on the LC-OCD results, even demineralized water backwashing is not effective to remove all humic substances and biopolymers rejected on the UF membranes.

Chapter 1: An overview of allergens

Most allergens are proteins or glycoproteins that range in molecular weight from 5000 to 100,000 Da, although polysaccharides and low molecular weight substances also may be allergenic. Common allergens include pollens, fungal spores, house-dust mites, and animal epithelial materials but can also include drugs, biological products, and insect venoms. The allergic response is dependent on the route of exposure. If exposure is to an inhaled aeroallergen, the allergic response will be a respiratory reaction in nature. Ingested or injected exposure gives rise to gastrointestinal, cutaneous, or anaphylactic reactions. Size of pollen determines clinical manifestation of allergy. For example, particles between 20 and 60 μm in diameter can be carried in the wind and cause nasal and ocular symptoms (allergic rhinoconjunctivitis). Particles <7 μm can deposit in the airways and cause symptoms of asthma. Animals produce allergens in forms unique to each species. Cat allergen, most importantly Fel d 1, is found mainly in cat saliva, sebaceous glands in the skin, and in urine of male cats. It is buoyant and "sticky," which means it easily remains airborne and may last in a home for up to 6-9 months after the source is removed. Cat allergen adheres to clothes and can be found in public places such as schools. Dog allergen, particularly Can f 1, is present in dander, saliva, urine, and serum. There are allergens specific to dog breeds, but all breeds produce allergenic proteins (even poodles and "hairless" dogs).

EFFECT OF MALEIC ANHYDRIDE ON KENAF DUST FILLED POLYCAPROLACTONE/THERMOPLASTIC SAGO STARCH COMPOSITES

The utilization of biodegradable polymers for various applications has been restricted mainly by its high cost. This report aims to study the water absorption and mechanical properties of kenaf dust-filled polycaprolactone/thermoplastic sago starch biodegradable composites as a function of filler loading and treatment with maleic anhydride. While water absorption in untreated biocomposites increased as a function of filler loading, treated biocomposites resulted in weight loss, whereby low molecular weight substances were dissolved into the aging medium. The kenaf dust imparts reinforcing effects on the biocomposites, resulting in improved mechanical properties. This is further attested by morphological studies in which kenaf dust was well dispersed in the polycaprolactone/ thermoplastic sago starch blend matrix. The addition of maleic anhydride into the polycaprolactone/thermoplastic sago starch blend resulted in a homogeneous mixture. At low filler loading, strain at break of the maleated polycaprolactone/thermoplastic sago starch blend increased at the expense of tensile strength and modulus. This is most likely due to the excessive dicumyl peroxide content, which caused chain scission of the polycaprolactone backbone. Tensile strength and modulus improved only when high filler loading was employed.

Bottom-up nanostructured metallic surfaces for SERS detection of low-molecular weight substances

Bottom-up nanostructured metallic surfaces for SERS detection of low-molecular weight substances

Glass transition and crystallization of low-temperature amorphous condensates of the water-propane mixture

Interest in gas hydrates stems from the existence of vast reserves of hydrocarbons on the earth in the form of gas hydrates, prospects for using them as a fuel source, and the possibility of storage and transporta� tion of gas in the gas hydrate state. The known meth� ods of production of gas hydrates are based on rela� tively small deviations from the equilibrium condi� tions of gas dissolution. They require the use of high pressures in laboratory or manufacturing equipment. For example, the pressure corresponding to the for� mation conditions of methane hydrate at temperatures near 0°С amounts to tens of bars. In addition, forma� tion of the crystal hydrate requires dispersion of water, which is afforded by longterm and vigorous stirring of the water-gas mixture. In this work, we have proposed another approach implying that hydrates are formed under conditions far from thermodynamic equilibrium. The approach is based on lowtemperature molecularbeam deposi� tion in a vacuum onto a surface cooled by liquid nitro� gen. During this process, amorphous (glassy) layers of the water-gas mixture are initially formed, which are stabilized by high viscosity. Heating of the amorphous layers is accompanied by avalanchetype nucleation and growth of gas hydrate crystallization sites. This method requires neither high pressures nor stirring of the water-gas system. Its advantage is that it is univer� sal and can be used for producing various gas hydrates. This work deals with studying the glass transition and crystallization of amorphous condensates of the binary water-propane system obtained by lowtem� perature condensation to determine the conditions of crystal hydrate formation. Amorphous solid (glassy) layers of lowmolecular� weight substances can be obtained by molecularbeam deposition onto a cooled surface. At low temperatures, the amorphous state of these substances is stabilized by the high viscosity. Molecularbeam deposition onto a copper substrate cooled by liquid nitrogen affords amorphous layers of water and simple molecular com� pounds (1), as well as of aqueous solutions of organic liquids (2). Cooling rates under these conditions are as high as 10 5 -10 7 K/s. On heating, the condensates undergo glass transition (softening) and subsequent spontaneous crystallization. In the course of the latter, a decisive role for phase transformation is played by homogeneous nucleation. The crystallization of amorphous water-gas condensates can result in the formation of gas hydrates (3-5). Hydrate formation is facilitated by the low chemical affinity of the hydrate� forming substance, as well as by the size and shape of its molecules corresponding to the geometry of cavi� ties in the arising clathrate framework. Among such substances, there are light hydrocarbons of the meth� ane series. Experiments with lowtemperature con� densates of the water-methane mixture showed the possibility of producing massive samples of crystal hydrates with high gas content capable of sustained burning (5).

Effect of Heptral on Blood Coagulant Activity in Pancreonecrosis

Objective: to attempt to reduce the hemostatic, detoxifying, and antioxidant dysfunctions of the liver in experimental pancreonecrosis and the degree of pancreatogenic endotoxemia, by using the hepatoprotector heptral. Materials and methods. Experiments were carried out on 142 outbred male rats divided into 3 groups: 1) control (n=20); 2) study (n=69); 3) comparison (n=53). Pancreonecrosis was simulated in the study and comparison groups. In Stage 1, coagulation hemostatic parameters were studied and the levels of low and medium molecular weight substances and the rate of free radical oxidation processes were determined. In Stage 2, five minutes after stimulation of pancreonecrosis, heptral was given in a dose of 11.4 mg/kg to the comparison animals, by studying the same parameters as in the study and control groups. The results were processed using the nonparametric statistical methods. Results. It has been found that hepatic detoxifying and antioxidant functions are impaired and free radical oxidation processes activated within 2 days after simulation of pancreonecrosis. Blood coagulation activity is considerably higher due to activated coagulation factors. Heptral increases the capacity of the liver to synthesize blood coagulation factors, which proves improvement of some of the study parameters of the hemostatic system. Furthermore, its administration preserves the antitoxic function of hepatocytes, as shown by the decreased concentrations of low and median molecular weight substances in plasma and red blood cells. At the same time, there is an increase in antioxidant system activity detectable by chemiluminescence which also testifies that hepatic functional and metabolic impairments are ameliorated. Key words: pancreonecrosis, liver, endotoxemia, hemo-stasis, free radical oxidation, heptral.

Impaired Iron Metabolism in the Pathogenesis of Critical Conditions (an Experimental Study)

Objective: to study the pathogenetic value of iron metabolic disturbances in microcirculatory disorders and in the development of endotoxemia in the critical conditions caused by abdominal sepsis and bone injury. Material and methods: Abdominal sepsis was simulated in the first series of experiments on 40 male Wistar rats; hip fracture of both hind limbs was done in 40 rats in the second series. In each series of experiments, deferoxamine was injected at a dose of 80 mg/kg in 10 animals for preventive purposes 2 hours before simulating the critical condition. The viscosity of blood and the levels of serum transferrin, ferritin, iron, oligopeptides, and low and medium molecular weight substances (LMMWS) were studied. Results. In severe bone injury and abdominal sepsis, there was a reduction in serum transferrin by more than 50%, impaired blood rheology, and increases in LMMWS and oligopeptides. Pre-administration of deferoxamine led to the normalization of transferrin concentrations and blood rheology, which was associated with lower serum Fe2+ concentrations. Conclusion. Thus, pre-administration of deferoxamine reduces impaired blood rheology and the intensity of endotoxemia in different critical conditions. Key words: critical conditions, iron metabolism, transferrin, microcirculatory disorders, endotoxemia, deferoxamine.

Anti-inflammatory and antioxidant effects of IMMUNEPOTENT CRP in Lipopolysaccharide (LPS)-stimulated human macrophages

IMMUNEPOTENT CRP is a mixture of low molecular weight substances, some of which have been shown to be clinically effective for a broad spectrum of diseases, maintaining the immune system and increasing the quality of life of the patients. To determine whether IMMUNEPOTENT CRP modulates the antioxidant and anti-inflammatory effects in LPS-stimulated human macrophages; U-937 cells were differentiated to macrophages with PMA (10 ng/mL), stimulated with LPS (50 ng/mL), and treated with IMMUNEPOTENT CRP (0, 0.5, 1, 3, and 5 U/mL). Thereafter, the antioxidant (Total antioxidant, CAT, GPx, and SOD), inflammatory (NO, TNF-a, COX-2, PGD2), IkB phosphorylation, and NF-kB DNA binding activities were evaluated by ELISA and colorimetric enzymatic assays. The IMMUNEPOTENT CRP significantly increased the Total antioxidant, CAT, GPx, and SOD activities, and significantly decreased the NO, and TNF-a production, COX-2 and PGD2activities, IkB phosphorylation, NF-kB p50 and p65 subunit DNA binding activity in LPS-stimulated human macrophages (*P<0.05). Our results demonstrated that IMMUNEPOTENT CRP plays an important role in modulating the antioxidant and anti-inflammatory effects through IkB/NF-kB pathway in LPS-stimulated human macrophages,suggesting that IMMUNEPOTENT CRP is an effective therapeutic agent in process involved in oxidative cellular damage and clinical inflammatory diseases. Key words: Dialyzable leukocyte extract, NF-kB, TNF-α.

Pharmacological and Biological Antiviral Therapeutics for Cardiac Coxsackievirus Infections

Subtype B coxsackieviruses (CVB) represent the most commonly identified infectious agents associated with acute and chronic myocarditis, with CVB3 being the most common variant. Damage to the heart is induced both directly by virally mediated cell destruction and indirectly due to the immune and autoimmune processes reacting to virus infection. This review addresses antiviral therapeutics for cardiac coxsackievirus infections discovered over the last 25 years. One group represents pharmacologically active low molecular weight substances that inhibit virus uptake by binding to the virus capsid (e.g., pleconaril) or inactivate viral proteins (e.g., NO-metoprolol and ribavirin) or inhibit cellular proteins which are essential for viral replication (e.g., ubiquitination inhibitors). A second important group of substances are interferons. They have antiviral but also immunomodulating activities. The third and most recently discovered group includes biological and cellular therapeutics. Soluble receptor analogues (e.g., sCAR-Fc) bind to the virus capsid and block virus uptake. Small interfering RNAs, short hairpin RNAs and antisense oligonucleotides bind to and led to degradation of the viral RNA genome or cellular RNAs, thereby preventing their translation and viral replication. Most recently mesenchymal stem cell transplantation has been shown to possess antiviral activity in CVB3 infections. Taken together, a number of antiviral therapeutics has been developed for the treatment of myocardial CVB infection in recent years. In addition to low molecular weight inhibitors, biological therapeutics have become promising anti-viral agents.

Hymenoptera Venom Proteins and Peptides for Diagnosis and Treatment of Venom Allergic Patients

Stings by insects of the order Hymenoptera cause systemic, sometimes life threatening allergic reactions in 1 - 5% of the population in Europe and North America. Responsible for these reactions is an IgE mediated sensitization to proteins of the venoms injected during the stings of social Hymenoptera species, mainly the honey bee (Apis mellifera), vespids like Vespula sp., Polistes sp. and ants, in southern US and central America Solenopsis invicta and in Australia Myrmecia pilosula. The venoms of these insects are composed of low molecular weight substances like biogenic amines, cytotoxic and neurotoxic peptides like melittin, apamin, MCD-peptide and mastoparan, and proteins, mostly enzymes like phospholipase A and hyaluronidase, which are major venom allergens. Immunotherapy with Hymenoptera venoms has been shown to protect 80 to over 95% of patients with a history of systemic allergic sting reaction from further systemic reactions after re-stings. The procedure, safety and efficacy of this treatment and the immune mechanisms involved are discussed. Since ancient times honey bee venom has been used for the treatment of chronic inflammatory disease, especially arthritis. Anti-inflammatory effects of bee venom have been documented in animal experiments. Most clinical studies suggest an antiinflammatory effect as well, but are uncontrolled. The only few controlled studies could not confirm efficacy of treatment with bee venom so far.

Origins and function of 3-ribosylurate in bovid erythrocytes

3-Ribosylurate is a dominant feature on high performance liquid chromatography (HPLC) profiles of acid extracts of erythrocytes from cows and buffalo, but is HPLC-undetectable in acid extracts of erythrocytes from all other species examined to date. Various aspects of this unique low molecular weight substance remain unexplored since it was first identified. In this study, the mutation(s) responsible for the appearance of ribosylurate in these cells is shown to be specific to members of both tribes of the Bovinae subfamily (Bovidae family), being detectable in the erythrocytes of both the cow and the buffalo (Bovini tribe) as well as in the kudu (Strepsicerotini tribe), but not in representative species from the other subfamilies of the Bovidae family. More specifically, expression of the mutation(s) seems to be restricted to the erythrocyte lineage of these species, ribosylurate being undetectable in cow white blood cells and primary cultures of fibroblasts. Novel evidence is presented that ribosylurate has antioxidant activity. Accumulation of high levels specifically within the haemoglobin-rich milieu of circulating erythrocytes may serve to protect perfused tissues by removing pathophysiological levels of hydrogen peroxide from plasma. Maintenance of ribosylurate levels may be important in conditions associated with oxidative stress in Bovinae.

Enhanced performance of a submerged membrane bioreactor with powdered activated carbon addition for municipal secondary effluent treatment

The aim of this study was to investigate the feasibility of PAC-MBR process treating municipal secondary effluent. Two laboratory-scale submerged MBRs (SMBR) with and without PAC addition were continuously operated in parallel for secondary effluent treatment. Approximately 63%TOC, 95% NH 4 +–N and 98% turbidity in secondary effluent were removed by the PAC-MBR process. Most organics in the secondary effluent were found to be low molecular weight (MW) substances, which could be retained in the reactor and then removed to some extent by using PAC-MBR process. Parallel experiments showed that the addition of PAC significantly increased organic removal and responsible for the largest fraction of organic removal. Membrane fouling analysis showed the enhanced membrane performance in terms of sustainable operational time and filtration resistances by PAC addition. Based on these results, the PAC-MBR process was considered as an attractive option for the reduction of pollutants in secondary effluent.

Nutrition Disorders During Acute Renal Failure and Renal Replacement Therapy

The physiological and biological modifications related to acute renal failure in critically ill patients, including the current use of continuous renal replacement therapies, have dramatically changed the type and importance of the metabolic and nutrition disturbances observed during treatment of renal failure. This review summarizes the current knowledge and makes recommendations for the daily nutrition management of these patients. The filtration of water-soluble substances of low molecular weight by continuous hemodiafiltration results in significant losses of glucose, amino acids, low-molecular-weight proteins, trace elements, and water-soluble vitamins. The losses of these macronutrients and micronutrients should be compensated for. During continuous renal replacement therapy, the daily recommended energy allowance is between 25 and 35 kcal/kg, with a ratio of 60%-70% carbohydrates to 30%-40% lipids, and between 1.5 and 1.8 g/kg protein. Providing energy 25-35 kcal/kg/d with a carbohydrate/lipid ratio of 60-70/30-40 and protein 1.5-1.8 g/kg/d is recommended during continuous renal replacement therapy. Supplemental vitamin B(1) (100 mg/d), vitamin C (250 mg/d), and selenium (100 mcg/d) are also recommended.

BPH Tranexamic acid decreases blood loss during transurethral resection of the prostate (TUR-P)

IntroductionPostoperative blood loss after prostate surgery is thought to be associated with an increase in urinary fibrinolytic activity. Tranexamic acid (TXA) is both a potent inhibitor of plasminogen and urokinase activators and a low molecular weight substance that is excreted unchanged in the urinary tract and can be administered both orally and intravenously. We investigated the effect of TXA on the amount of blood loss during transurethral resection of the prostate (TURP).Materials and methodsForty patients with registry numbers ending in even numbers were allocated to the treatment group; those ending in odd numbers were used as controls and received no treatment. The treatment group received 10 mg/kg TXA by intravenous infusion during the first half hour of the operation, while the control group of patients received no medication. Serum hemoglobin was measured before and after surgery. The volume and hemoglobin concentration of the irrigation fluid, resected prostate weight, and duration of resection were recorded.ResultsThe mean loss of hemoglobin per gram of resected prostate tissue was 1.25 g in the TXA group and 2.84 g in the control group. Total hemoglobin loss in the irrigating fluid and hemoglobin loss per 1 gram of prostate tissue was lower in the group of patients given TXA than in the control group (p = 0.018 and p <0.001).ConclusionReduced bleeding during TURP as a result of TXA treatment may lead to better surgical conditions and, as a consequence, shorter operative times and lower irrigating fluid volumes.

Study of α-Crystallin Structure by Small Angle Neutron Scattering with Contrast Variation

The structure of the oligomeric protein α-crystallin from bovine eye lens was investigated by small-angle neutron scattering (SANS) with contrast variation. Based on the SANS curves, the match point for α-crystallin (43% D2O) and its average scattering length density at this point (2.4·10(10) cm(-2)) were evaluated. The radius of gyration and the distance distribution functions for α-crystallin were calculated. On the basis of these calculations, it was concluded that α-crystallin is characterized by homogeneous distribution of scattering density in the domains inaccessible for water penetration, and all polypeptide subunits in α-crystallin oligomers undergo equal deuteration. The latter indicates that all α-crystallin subunits are equally accessible for water and presumably for some other low molecular weight substances. These conclusions on the α-crystallin structure (homogeneous distribution of scattering density and equal accessibility of all subunits for low molecular weight substances) should be taken into account when elaborating α-crystallin quaternary structure models.

Evaluation of Dialyzer Jacket Structure and Hollow‐Fiber Dialysis Membranes to Achieve High Dialysis Performance

The objective of this study was to determine the optimum dialyzer jacket structure and hollow-fiber dialysis membrane, both of which are indispensable factors for achieving high dialysis performance, by clarifying the relationship between the dialysis performance and the flow of dialysate and blood in a hollow-fiber dialyzer. We evaluated the clearance, dialysate, and blood flow for four commercially available hollow-fiber dialyzers, namely, the APS-15S, APS-15SA, TS-1.6UL, and CX-1.6U. To evaluate dialysate and blood flow, we measured the residence-time distribution of dialysate and blood flow of these dialyzers by the pulse-response method. We also determined the clearances of urea, creatinine, vitamin B(12), and lysozyme to evaluate the dialysis performance of these dialyzers. While the baffle and taper structures allow effective supply of dialysate into the dialyzer jacket, the hollow-fiber shape, inner diameter, and packing density significantly influence the dialysate flow. In dialyzers with long taper-holding slits, the slit area is a key design parameter for achieving optimum dialysate flow. Similarly, the blood flow is significantly influenced by the structure of the inflowing and outflowing blood ports at the header of a dialyzer, and the shape and inner diameter of the hollow fibers. Hollow fibers with smaller inner diameters cause an increase in blood pressure, which causes blood to enter the hollow fibers more easily. The hollow-fiber shape hardly affects the blood flow. While improved dialysate and blood flow cause higher clearance of low molecular-weight substances, higher membrane area and pure-water permeability accelerate internal filtration, thereby causing an increase in the clearance of large molecular-weight substances.