Heart rate variability, salivary cortisol and competitive state anxiety responses during pre-competition and pre-training moments.

The study aimed to investigate physiological and psychological states prior to competition and prior to training in three different demanding activities. Eighteen canoe athletes, 18 street runners and 18 jiu-jitsu fighters were included in this study (n=54). The Competitive State Anxiety Inventory-2 (CSAI-2), salivary cortisol and heart rate variability (HRV) were measured at two time points (pre-training and pre-competition). Somatic anxiety (F1,42 = 15.29, p = 0.0003), HRV (F1,42 = 23.24, p < 0.0001) and salivary cortisol (F1,42 = 22.96, p < 0.0001) were significantly greater at the pre-competition measurement point than at the pre-training point, but without a main effect of the type of athlete on these variables. A main effect of the type of athlete was found on somatic anxiety (F2,42 = 6.58, p = 0.0033), cognitive anxiety (F2,42 = 10.69, p = 0.0002) and self-confidence (F2,42 = 5.42, p = 0.0080). Correlations between most CSAI-2 and physiological parameters were not significant (p > 0.05). In conclusion, the results indicated that both emotional indices and psychophysiological indices of stress are higher before competition than before training, with differences between emotional states between these sports. Although correlations between emotional states and psycho-physiological states before competition and before training were largely non-significant, these findings reinforce the importance of psychological monitoring of athletes in association with traditional physiological markers such as cortisol and HRV in sportive training programmes as complementary resources to improve both competition performance and the training routine.

Treinamento concorrente: Endurance x Força / Concurrent training: Endurance vs. Strength

Os efeitos do treinamento concorrente (TC) têm sido investigados desde a década de 80. Contudo, ainda existem muitas controversas sobre o seu efeito crônico. O objetivo deste estudo foianalisar trabalhos que compararam o comportamento de variáveis relacionadas à morfologia e a performance após a realização do TC. Para tal, foram selecionados 26 artigos no PubMed, SciELO, LILACS e no Google Acadêmico que estudaram seu efeito crônico em seres humanos adultos. Após análise dessas pesquisas verificou-se que as amostras utilizadas foram em ambos os sexos, com um quantitativo de 12 a 50 voluntários. O período de treinamento variou entre 7 e 21 semanas com uma frequência semanal de 2 a 6 dias por semana. Nenhum dos estudos utilizou dieta específica ou relataram o uso de suplementação pelos participantes durante as intervenções. Em relação aos tipos de treinamento observou-se que o TC é capaz de proporcionar uma manutenção ou melhora da composição corporal, reduzindo o percentual de gordura e aumentando a massa magra. O mesmo ocorreu em relação ao VO2máx, assim como o treinamento de endurance. Em relação à força máxima, todos os estudos apresentaram um aumento significante após a realização do TC e do Treinamento de Força (TF), mas em altas velocidades, como na potência, em alguns casos apenas houve a manutenção dos valores iniciais para o TC e o aumento no TF. Embora o TC possa não ser compatível com o desenvolvimento da potência, quando se discute seus benefícios relacionados à saúde, ele se mostrou eficaz...(AU)

The effects of concurrent training (CT) have been investigated since the 1980s. However, there are still many controversies about its chronic effect. The purpose of this research was to analyze studies comparing the behavior of variables related to morphology and performance after CT. For that, 26 articles were selected in PubMed, SciELO, LILACS and in Google Scholar that studied its chronic effect in adult humans. After analyzing these studies, it was verified that the samples used were in both sexes, with a quantitative of 12 to 50 volunteers. The training period ranged from 7 to 21 weeks with a weekly frequency of 2 to 6 days per week. None of the studies used a specific diet or reported the use of supplementation by participants during interventions. Regarding the types of training, it was observed that the CT is capable of maintaining or improving body composition, reducing fat percentage and increasing lean mass. The same occurred in relation to VO2max, as well as endurance training. Regarding the maximum force, all the studies presented a significant increase after the accomplishment of the CT and the Strength Training (ST), but in high speeds, as in the power, in some cases only the initial values were maintained for the CT and the increase in ST. Although CT may not be compatible with the development of potency, when discussing its health-related benefits, it has been shown to be effective...(AU)

A quantitative recipe for engineering protein polymer nanoparticles.

Protein polymers can assemble switchable nanostructures with emerging applications as biomaterials and nanomedicines. For example, above a critical micelle temperature (CMT) some elastin-like polypeptide (ELP) diblock copolymers assemble spherical nanoparticles, which may modulate cellular internalization and in vivo biodistribution. To achieve engineering-level control over their properties, this report explores a comprehensive library of ELP monoblock and diblock polymers. For the first time, we report that a surprisingly high core molecular weight is required for stable nanoparticle formation; furthermore, nanoparticle size depends on polymer molecular weight. A mathematical model was developed to characterize four ELP monoblock libraries and to predict the phase behavior of corresponding diblock copolymers. The CMT was almost entirely dependent on the hydrophobic core ELP, while the bulk phase transition temperature (Tt,bulk ) depends predominantly on the hydrophilic block. Nanoparticle assembly was accompanied by a conversion in secondary structure of the hydrophobic block from random coil and beta-sheets to type-2 ß turns. For the first time, this report enables the rational design of ELP protein polymer nanoparticles with physico-chemico properties that will be suitable for biological applications.

Comparison of particulate number concentrations in three Central European capital cities.

Number size distributions of atmospheric aerosol particles in the mobility diameter range from 10 to 1000 nm were determined in Budapest, Prague and Vienna for a one-year-long period. Particle number concentrations in various size fractions, their diurnal and seasonal variations, mean size distributions and some properties of new particle formation events were derived and compared. Yearly median particle number concentrations for Budapest, Prague and Vienna were 10.6×10(3), 7.3×10(3) and 8.0×10(3) cm(-3). Differences were linked to the different pollution levels of the cities, and to diverse measurement environments and local conditions. Mean contributions of ultrafine particles (particles with a mobility diameter <100 nm) to the total number concentration were 80%, 84% and 74% for Budapest, Prague and Vienna, thus these particles represent an overwhelming share of all particles in each city. Seasonal variation of particle number concentrations was not obvious. Diurnal variations of particles with a diameter between 100 and 1000 nm (N(100-1000)) exhibited similar shape for the cities, which was related to the time-activity pattern of inhabitants and regional influences. The structure of the diurnal variation for ultrafine particles was also similar. It contained a huge morning peak in each city which was explained by emissions from vehicular traffic. The second peak was shifted from afternoon rush hours to late evenings as a result of the daily cycling in meteorological parameters. The character of the measurement site also influenced the diurnal variation. Diurnal variation of the mean ratio of ultrafine particles to N(100-1000) clearly revealed the presence and importance of new particle formation and subsequent growth in urban environments. Nucleation frequencies in Budapest and Prague were 27% and 23%, respectively on a yearly time scale. They showed a minimum in winter for both places, while the largest nucleation activity was observed in spring for Budapest, and in summer for Prague.

Morphology of glomerular hematuria is reproduced in vitro by carbonyl stress.

BACKGROUND: In glomerulonephritides, dysmorphic red blood cells (RBCs) with membrane blebs can be found in the urine; this is referred to as glomerular hematuria. Glomerulonephritides are characterized by increased carbonyl stress and elevated methylglyoxal (MGO) levels. MGO causes oxidative stress and intracellular calcium accumulation. In the present study, we investigated whether the effect of MGO-induced calcium accumulation in RBCs develops through increased oxidative stress. Furthermore, we studied whether MGO can lead to RBC membrane blebbing. METHODS: RBC suspensions from healthy volunteers were incubated with different concentrations of MGO at 37 degrees C. We measured oxidative stress and intracellular calcium level using fluorescent indicators. We determined the frequency of dysmorphic RBCs, and also performed scanning electron microscopy. RESULTS: MGO increased oxidative stress and caused accumulation of calcium in isolated RBCs. These effects could be prevented using antioxidants. In the presence of MGO, RBC membrane blebbing developed. CONCLUSION: According to our findings, MGO causes calcium accumulation through oxidative stress. Carbonyl and oxidative stress may play an important role in the formation of dysmorphic RBCs in glomerular hematuria.

Cigarette smoke-induced alterations in endothelial nitric oxide synthase phosphorylation: role of protein kinase C.

Endothelial nitric oxide synthase (eNOS) is regulated by phosphorylation of Ser(1177) and Thr(495), which affects NO bioavailability. Cigarette smoke disturbs the eNOS-cGMP-NO pathway and causes decreased NO production. Here the authors investigated the acute effects of cigarette smoke on eNOS phosphorylation, focusing on protein kinases (PKs). Endothelial cell culture was concentration- and time-dependently treated first with cigarette smoke buffer (CSB), then with reduced glutathione (GSH) or various PK inhibitors (H-89, LY-294002, Ro-318425, and ruboxistaurin). eNOS, phospho-Ser(1177)-eNOS, phospho-Thr(495)-eNOS, Akt(PKB), and phospho-Akt protein levels were determined by Western blot. CSB increased the phosphorylation of eNOS at Ser(1177) and more at Thr(495) in a concentration- and time-dependent manner (p < .01, p < .05 versus control, respectively) and resulted in the dissociation of the active dimeric form of eNOS (p < .05). GSH decreased the phosphorylation of eNOS at both sites (p < .05 versus CSB without GSH) and prevented the decrease of dimer eNOS level. CSB treatment also decreased the level of phospho-Ser(473)-Akt (p < .05 versus control). Inhibition of PKA by H-89 did not affect CSB-induced phosphorylation, whereas the PKB inhibitor LY-294002 enhanced it at Ser(1117). The PKC blockers Ro-318425 and ruboxistaurin augmented the CSB-induced phosphorylation at Ser(1177) but decreased phosphorylation at Thr(495) (p < .05 versus CSB). Cigarette smoke causes a disruption of the enzymatically active eNOS dimers and shifts the eNOS phosphorylation to an inhibitory state. Both effects might lead to reduced NO bioavailability. The shift of the eNOS phosphorylation pattern to an inhibitory state seems to be independent of the PKA and phosphoinositol 3-kinase (PI3-K)/Akt pathways, whereas PKC appears to play a key role.

Single dose of acetylsalicylic acid in patients with Type 2 diabetes mellitus and/or chronic renal failure ameliorates anaemia by decreasing the rate of neocytolysis.

BACKGROUND: Anaemia in diabetes mellitus (DM) and/or chronic renal failure (CRF) may be caused by a decreased production of erythropoietin (EPO), EPO resistance, and by the lysis of the young circulating red blood cells (neocytolysis) induced by subclinical inflammation and low EPO level. Aims of this study were to detect EPO resistance in patients with DM and/or CRF and to prove, that acetylsalicylic acid (ASA) is able to improve the haemopoietic status by decreasing neocytolysis. METHODS: In a cross-sectional study, three groups of selected patients (patients with DM; patients with DM+CRF; patients with CRF without DM, n=15 each) and a group of controls (non-diabetic, nonazotemic subjects, n = 10) were compared. In the intervention part of the study, the effect of a single dose of 1 gram ASA on neocytolysis was investigated in a subgroup of these patients. RESULTS: Despite the similar EPO level (p = 1.000), all three patient groups had lower haemoglobin and haematocrit than control persons (p < 0.05 in all cases). Patients with DM+CRF had lower haemoglobin than patients with DM or CRF alone (p < 0.05). Single dose of ASA induced a fast increase in serum EPO level, a concomitant rise of the Rtc number and rate, red blood cell count, haematocrit and haemoglobin p < 0.01 for each). These changes were accompanied by a marked decrease in serum lactate dehydrogenase activity (p < 0.01). CONCLUSIONS: DM and CRF may induce erythropoietin resistance. In these patients, ASA treatment increases serum EPO level. The higher EPO level and the anti-inflammatory effect of ASA may decrease neocytolysis.

Oxidative stress and non-enzymatic glycation in IgA nephropathy.

AIM: Approximately 20-50% of IgA nephropathy patients develop end-stage renal disease. We have previously found enhanced oxidative stress and decreased antioxidant capacity in red blood cells of IgA nephropathy patients. In this study we assess oxidative stress, non-enzymatic glycation, oxidative resistance of low-density lipoprotein and its alpha-tocopherol content in these patients. PATIENTS AND METHODS: Non-enzymatic glycation and oxidative stress were assessed in 88 IgA nephropathy patients by measuring advanced glycation end products, Nepsilon-carboxymethyl-lysine, thiobarbituric acid reactive substances, oxidative resistance of low-density lipoprotein and its alpha-tocopherol content. RESULTS: Advanced glycation end products (2659 +/- 958 a.u.) and Nepsilon-carboxymethyl-lysine (563 +/- 215 ng/ml) were significantly higher in IgA nephropathy patients with decreased renal function compared to those with normal renal function (p < 0.002) or controls (p < 0.001). Thiobarbituric acid-reactive substances in plasma and associated with low-density lipoprotein were significantly elevated and oxidative resistance of low-density lipoprotein was significantly reduced in all groups of IgA nephropathy patients. There was no significant difference in circulating fluorescent advanced glycation end products, Nepsilon-carboxymethyl-lysine, thiobarbituric acid-reactive substances levels, oxidative resistance of low-density lipoprotein and its alpha-tocopherol content between patients with normal vs. impaired glucose metabolism. Low alpha-tocopherol content of low-density lipoprotein was accompanied with decreased oxidative resistance, depletion in polyunsaturated fatty acids, elevated saturated fatty acids and thiobarbituric acid-reactive substances within low-density lipoprotein suggesting enhanced lipid peroxidation. CONCLUSIONS: Decreased oxidative resistance of low-density lipoprotein and enhanced oxidative stress are common features in IgA nephropathy, while increased non-enzymatic glycation occurs as renal function declines.

Cigarette smoke and its formaldehyde component inhibit bradykinin-induced calcium increase in pig aortic endothelial cells.

Bradykinin-induced increase in the intracellular concentration of free calcium evokes an activation of the endothelial nitric oxide synthase (eNOS) enzyme, producing nitric oxide (NO). Cigarette smoke inhibits the eNOS-NO-cGMP signaling pathway. The pathomechanism of this deleterious effect of smoke on NO production is unknown. The aim of this study was to investigate the effect of gas phase smoke trapped in a buffer (smoke buffer, SB) on the bradykinin-induced calcium increase in cultured endothelial cells. FURA-2-AM was used to detect bradykinin-induced calcium increase. A sensitive, fluorescent method using O-phthaldialdehyde was used for the determination of intracellular reduced glutathione (GSH) and protein-thiol levels. SB caused a time- and concentration-dependent inhibition of bradykinin-induced calcium increase. Formaldehyde, a component of SB, inhibited bradykinin-induced calcium increase in concentrations characteristic for SB. SB decreased both the intracellular GSH (0.22 +/- 0.06 vs. 2.23 +/- 0.32 mumol/g protein, SB vs. control, p < .001) and protein-thiol levels (4.98 +/- 0.54 vs. 7.31 +/- 0.97 microEqu GSH/g protein, SB vs. control, p < .05) in the endothelial cells. Intracellular GSH and protein-thiol levels were not changed by 80 microM formaldehyde. GSH (4 mM) prevented the effect of SB (p < .001) and formaldehyde (p < .05) on the bradykinin-induced calcium increase. Our data support the premise that SB inhibits bradykinin-induced calcium increase. This inhibition is partially due to protein-thiol oxidation but may also be caused by the formaldehyde content of SB, which inhibits calcium increase in a protein-thiol-independent manner.

Role of iron in the interaction of red blood cells with methylglyoxal. Modification of L-arginine by methylglyoxal is catalyzed by iron redox cycling.

Diabetes mellitus is characterized by increased methylglyoxal (MG) production. The aim of the present study was to investigate the role of iron in the cellular and molecular effects of MG. A red blood cell (RBC) model and L-arginine were used to study the effects of MG in the absence and presence of iron. Intracellular free radical formation and calcium concentration were measured using dichlorofluorescein and Fura-2-AM, respectively. Effects of MG were compared to the effect of ferrous iron. Reaction of L-arginine with MG was investigated by electron spin resonance (ESR) spectroscopy and by a spectrophotometric method. MG caused an iron dependent oxidative stress in RBCs and an elevation of the intracellular calcium concentration due to formation of reactive oxygen species. Results of co-incubation of MG with ferrous iron in the RBC model suggested an interaction of MG and iron; one interaction was a reduction of ferric iron by MG. A role of iron in the MG-L-arginine reaction was also verified by ESR spectroscopy and by spectrophotometry. Ferric iron increased free radical formation as detected by ESR in the MG-L-arginine reaction; however, ferrous iron decreased it. The reaction of MG with L-arginine yielded a brown product as detected spectrophotometrically and this reaction was catalyzed at a lower rate with ferric iron but at a higher rate with ferrous iron. These data suggest that MG causes oxidative stress in cells, which is due at least in part to ferric iron reduction by MG and to the modification of amino acids e.g. L-arginine by MG, which is catalyzed by iron redox cycling.

Insulin-induced peroxynitrite production in human platelet-rich plasma.

Recent data support the possible role of nitric oxide (NO*) in the development of insulin signalling. The aim of this study was to examine the effect of insulin on NO* production by platelets. The chemiluminescence of platelet-rich plasma prepared from the blood of healthy volunteers was measured in the presence of luminol. Indirect detection of NO* by luminol is possible in the form of peroxynitrite produced in the reaction of NO* with a superoxide free radical. Luminol oxidation induced by hydroxyl free radical and lipid peroxidation was prevented by 150 micromol/l of desferrioxamine mesylate. Insulin, in the range of 0.084-840 nmol/l, induced a concentration-dependent increase in chemiluminescence, which was inhibited both by the competitive antagonist of the NO* synthase enzyme. N(omega)-nitro-L-arginine methyl ester (at concentrations of 2.0-4.0 mmol/l, P<0.001), and by the elimination of superoxide free radicals using superoxide dismutase (72-144 IU/ml, P<0.001). In conclusion, we assume that the insulin-induced increase in chemiluminescence of platelet-rich plasma was due to increased production of NO* and superoxide free radicals forming peroxynitrite. The data are consistent with production of peroxynitrite from human platelets under insulin stimulation.

N(epsilon)-(carboxymethyl)lysine levels in patients with type 2 diabetes: role of renal function.

Advanced glycation end products (AGEs) such as N(epsilon)-(carboxymethyl)lysine (CML) have been implicated in the development and progression of diabetic nephropathy. The aim of the present study is to investigate AGE levels in patients with type 2 diabetes with special regard to the role of renal impairment. Serum and urine CML levels (using a newly developed enzyme-linked immunosorbent assay), as well as serum AGE-fluorescence, were measured in 109 patients with type 2 diabetes. Patients were divided into groups with normal and impaired renal function. We found elevated serum fluorescent AGE and CML levels, as well as decreased urinary CML excretion rates, in patients with diabetes with renal impairment, but not those with normal renal function. In the presence of impaired renal function, serum CML and fluorescent AGE levels showed a significant inverse relation with creatinine clearance and a significant direct correlation with each other. No relationship could be found between serum AGE levels and parameters of blood glucose control or the presence of the following clinical complications: ischemic heart disease, diabetic retinopathy, and neuropathy. We conclude that the decline in renal function leads to increased serum AGE levels in patients with type 2 diabetes.

[Detection of glycation end products in the urine of diabetic patients]. / Glikációs végtermékek kimutatása diabetes mellitusban szenvedö betegek vizeletében.

Advanced glycation end products play an important role in the development of tissue damage in diabetes mellitus. The aim of the present study was the investigation of the excretion of different glycation end products in the urine. Methylglyoxal, an intermediate product of the glycation, formed with L-arginine in an in vitro model two fluorescent peaks. These peaks can be characteristic for imidazolone-like product(s) which are produced also in the reaction of methylglyoxal with proteins described in the literature, suggesting modification of proteins with methylglyoxal at the guanidino group of the L-arginine amino acid. Using the fluorescent characteristics of these (excitation/emission: 320/400 nm and 340/425 nm) and the generally accepted wavelength of the so called non-specific advanced glycation end product (370/440 nm) could be identified these glycation end products in the urine of 98 patients with diabetes mellitus (21 type I., 77 type II., 51 female and 47 male, mean age: 56.6 years). These three particular glycation end products showed significant intercorrelations in the urine (p < 0.001). Concentrations of these glycation end products in the urine correlated negatively with the serum creatinine in the range between 120-240 mumol/l (p < 0.001). Data presented here verify that non-specific glycation end product and imidazolone-like glycation end products can be detected in the urine of diabetic patients. Elimination of these products by the urine is markedly decreased in the stage of early renal insufficiency. These decrease in the secretion can cause an elevation of the advanced glycation end products in the circulation leading progression of diabetic complication.

[Detection of carbonyl stress markers in the urine of diabetic patients]. / Karbonil stressz-metabolitok kimutatása diabetes mellitusban szenvedö betegek vizeletében.

Carbonyl stress-induced tissue damage is caused by reactive aldehydes produced by non-enzymatic glycation, oxidative stress and metabolic processes. The aim of this study was the detection of the major markers of carbonyl stress in the urine of diabetic patients (21 type 1, 77 type 2, 51 female, 47 male, 56.6 +/- 13.7 year of age; mean +/- SD). Oxidative stress was detected by using the reaction of malondialdehyde, the end product of free radical damage of the tissues, with L-arginine. This reaction produced a fluorescent compound, pyrimidinyl-L-ornithine. Thus, pyrimidinyl-L-ornithine, as well as pentosidine, an advanced glycation end product, and the non-specific advanced glycation end product, which is thought to be partially as a result of lipid peroxidation, could be detected simultaneously by using the fluorescent method. Correlation coefficients among the concentrations of these products in the urine of 98 diabetic patients were as follows: pyrimidinyl-L-ornithine vs. non-specific advanced glycation end product: r = 0.72, p < 0.001; pentosidine vs. non-specific advanced glycation end product: r = 0.68, p < 0.001; pentosidine vs. pyrimidinyl-L-ornithine: r = 0.60, p < 0.001. Strong negative correlations were found between the serum creatinine levels of these patients, between 120-240 mumol/l, and the urinary concentration of these products: r = -0.88 for non-specific advanced glycation end products, r = -0.86 for pentosidine and r = -0.89 for pyrimidinyl-L-ornithine (p < 0.001 for all three). These data support a closer relation of the so-called non-specific glycation end product to oxidative stress than to non-enzymatic glycation. Results presented here suggest an early retention of the products of carbonyl stress in the patients with moderate renal insufficiency, which can play a role in the development of diabetic complications.

Pharmacokinetics and retrograde colonic spread of budesonide enemas in patients with distal ulcerative colitis.

METHODS: The retrograde spread of two budesonide enema formulations with different viscosities was investigated. The study design was open, randomized and two-period crossover. Three female and two male patients (age range: 35-45 years) with distal ulcerative colitis or proctitis participated. Both enema formulations contained a dose of 2 mg budesonide/100 mL. An unabsorbable radioactive marker (99mTc-labelled human serum albumin microcolloid) was added to the enema just before administration. All doses were given in the evening with the patients lying in a supine position during the whole investigation. The intestinal spread was followed for 8 h using scintigraphic imaging. Plasma samples for budesonide assay were taken during the 12 h after administration of the low viscosity enema. RESULTS: Budesonide plasma levels were measurable for up to 4-6 h. Cmax was 2.5 nmol/L (range: 0.9-4.5 nmol/L) and was attained in 1.5 h (range 1-3 h). The patients had no difficulty in retaining the enemas. There was a statistically significant difference in spread between the low and high viscosity enema. The low viscosity enema spread over an area situated between the rectum and the splenic flexure. The spread occurred mainly in the first 15 min after administration. In contrast, the high viscosity enema, in most cases, spread only over a minor part of this area and the rate and extent of spreading was also more variable with this formulation. CONCLUSION: The spread of a low viscosity enema appears to be well suited for the treatment of proctitis and distal colitis.

Plasma concentrations of remoxipride and the gastrointestinal transit of 111In-marked extended-release coated spheres.

To explore the oral absorption of remoxipride, spheres of remoxipride were labeled with indium-111 colloid before coating with a release-controlling ethylcellulose membrane. Since the labeling remained inside the coating, it was suitable as a marker. Eight healthy volunteers were given a single dose of 100 mg remoxipride in 111In-marked spheres as a multiple-unit capsule. The radioactivity and the position of the spheres (microcapsules) were followed externally for 30 hr by gamma scintigraphy. Parallel to this, plasma concentrations were drawn for 48 hr to confirm the extended dissolution and absorption of remoxipride. The hard gelatin, multiple-unit capsule released the microcapsules within the stomach. These were then rapidly emptied into the small intestine, within 0.5-1 hr. There was then an immediate distribution in the upper small intestine before collection in the lower portion, within 2-5 hr. After passing into the large intestine, there was again extended distribution of the microcapsules. A mean Cmax of 2.7 microM remoxipride was achieved 4 hr after drug administration and a mean AUC of 26.1 mumol.L-1.hr was achieved. Judging from the absorption versus time profile, calculated according to the Wagner-Nelson method, and the scintigraphic images, it is concluded that the main absorption occurs from the small intestine. Data from four volunteers, however, indicated a comparatively good absorption also from the large intestine. Due to the good absorption properties, it is reasonable to expect a low variation in the extent of bioavailability of remoxipride after administration in an extended-release, multiple-unit capsule formulation.

Acute lung injury monitored with radiolabeled transferrin and lung volume measurements.

Anesthetized pigs (n = 12) were given oleic acid (OA) to induce acute lung injury. Three additional pigs were used as uninjured controls. Six of the animals were pretreated with terbutaline before OA infusion. 113mIn-labeled transferrin and 99mTc-labeled erythrocytes were used for tracing of extravascular plasma leakage. A computerized gamma camera supplied image analysis of the radioactivities over the heart and lungs. A lung transferrin index (LTI), which describes the net accumulation of plasma equivalents in the lung, was calculated. OA caused an immediate increase in LTI and concurrent, correlated decreases in functional residual capacity, lung thorax compliance and arterial PO2. LTI was also correlated to the content of plasma equivalents in lung tissue samples and also to the wet weight/dry weight-ratios of the same tissue samples. Finally, LTI was correlated to the calculated plasma loss from the circulation. Changes in all these parameters were correlated to the dose of OA. We conclude that this noninvasive double radioisotope technique can detect plasma protein leakage in lung injury of different degrees. We found no significant anti-edema effect of terbutaline.

A comparative distribution study of two procedures for administration of nose drops.

The intranasal distribution of nose drops has been studied in 12 healthy subjects, comparing an administration followed by two rapid inhalations through the nose, with an administration followed by turning the head to five positions. Insoluble particles of human serum albumin labelled with 99Tcm were suspended in the liquid before administration. A significantly larger area (p less than 0.05) in the nasal cavity was covered by the labelled nose drops when the subjects used the turning-the-head procedure. It appears that this procedure gave a larger passive distribution of the particles. The differences were about 10 to 15% between 3 and 45 min after administration. Some particles were rapidly transported into the pharynx. The retention of the particles at the initial site of deposition did not differ significantly between the two procedures and about 50% of the particles seemed to have penetrated to the ciliated region in the main nasal passages and were cleared. The results indicate that the procedure for administration of the nose drops influences the distribution in the nasal cavity, but the clinical relevance should be studied with respect to the efficacy of the active drug in patients.

Effect of viscosity on particle size, deposition, and clearance of nasal delivery systems containing desmopressin.

The effect of methylcellulose on the particle size distribution and dosing accuracy of pre-metered spray pump devices containing the peptide desmopressin (DDAVP) was investigated. Using gamma scintigraphy, the influence of methylcellulose on the in vivo deposition and clearance of nasal solutions administered as drops or spray was studied. Nasal formulations containing 0, 0.25, and 0.50% methylcellulose produced a dose-related increase in average particle size from 51 micron for 0% to 81 and 200 micron for 0.25 and 0.50% methylcellulose, respectively. However, no effect was observed on the dosing accuracy of the spray pumps. The addition of methylcellulose gave a more localized in vivo deposition in the anterior region of the nasal vestibule. However, the net effect on clearance followed a biphasic pattern which showed an increase in retention time for the 0.25% solution, followed by a decrease in retention time and faster clearance time for the 0.50% solution. The spray delivers well-controlled doses to the nasal cavity. These findings show that viscosity, particle size, and nasal clearance are important parameters in the design of nasal delivery systems.