bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanisms of intercellular hypertonicity and isotonic fluid absorption in proximal tubules of mammalian kidneys
Authors: KIIL F. 
Published: March 2003

ABSTRACTThe main purpose of this theoretical analysis (second of two articles) is to examine whether transjunctional diffusion of NaCl causes intercellular hypertonicity, which permits transcellular water transport across solute‐impermeable lateral cell membranes until osmotic equilibration. In the S2 segment with tubular NaCl concentration 140 mM, the calculated apical intercellular NaCl concentration is c0 ≈ 132 mM, which exceeds peritubular NaCl concentration by 12 mM or 22 mOsm kg–1. Variations in volume flow, junctional reflection coefficient (σNaCl=0.25–0.50), gap distance (g=6–8 Å), junctional depth (d=18–100 Å), intercellular diffusion coefficient (DLIS=500–1500 μm2 s–1) and hypothetical active NaCl transport alter c0 only by a fraction of 1 mM. However, dilution and back‐leakage of NaHCO3 lower apical intercellular hyperosmolality to ≈18 mOsm kg–1. Water transport through solute‐impermeable lateral cell membranes continues until intercellular and cellular osmolalities are equal. Transcellular and transjunctional volume flow are of similar magnitude (2 nL min–1 mm–1 tubule length) in the S2 segment. Thus, diffusion ensures isotonic absorption of NaCl. Two‐thirds of NaHCO3 and other actively transported sodium salts are extruded into the last third of the exponentially widening intercellular space where the exposure time is only 0.9 s. Osmotic equilibration is dependent on aquaporins in the cell membranes. If permeability to water is low, transcellular water transport stops; tubular fluid becomes hypotonic; NaCl diffusion diminishes, but transjunctional water transport remains unaltered as long as transcellular transport of NaHCO3 and other solutes provides the osmotic force.
Regulation of apical transporter of L‐DOPA in human intestinal Caco‐2 cells
Authors: FRAGA S. , SAMPAIO‐MAIA B. , SERRÃO M. P. , SOARES‐DA‐SILVA P. 
Published: March 2003

ABSTRACTThe present study examined the nature of the apical inward L‐3,4‐dihydroxyphenylalanine (L‐DOPA) transporter in human intestinal epithelial Caco‐2 cells, and whether protein kinases modulate the activity of this transporter. The apical inward transfer of L‐DOPA was promoted through an energy‐dependent and sodium‐insensitive transporter (Km=33 μM; Vmax=2932 pmol/mg protein/6 min). This transporter was insensitive to N‐(methylamino)‐isobutyric acid, but competitively inhibited by 2‐aminobicyclo(2,2,1)‐heptane‐2‐carboxylic acid (BCH; IC50=83 μM). The organic cation inhibitor decynium 24 failed to affect the accumulation of L‐DOPA, whereas the organic anion inhibitor 4,4′‐diisothiocynatostilbene‐2,2′‐disulphonic acid (DIDS) competitively inhibited L‐DOPA uptake (IC50=83 μM). However, the apical‐to‐basal and basal‐to‐apical transepithelial transport and the cell accumulation of [3H]‐PAH was close to that of [14C]‐sorbitol and insensitive to DIDS (300 μM). Modulators of protein kinase A (PKA) [cyclic adenosine monophosphate (cAMP), forskolin, H‐89 and cholera toxin], protein kinase G (PKG) [cyclic guanosine monophosphate (GMP), zaprinast, LY 83583 and sodium nitroprusside] and protein kinase C (PKC) (phorbol 12,13‐dibutirate and chelerythrine) failed to affect the accumulation of L‐DOPA. The Ca2+/calmodulin inhibitors calmidazolium and trifluoperazine inhibited L‐DOPA uptake (IC50s of 53 and 252 μM, respectively), but the rise of intracellular Ca2+ by A23187 (1 μM) and thapsigargin (1 μM) played no role on L‐DOPA uptake. It is concluded that Caco‐2 cells take up L‐DOPA over the apical cell border through the sodium‐independent and pH‐sensitive L‐type amino acid transporter.
Intracellular sodium modulates the state of protein kinase C phosphorylation of rat proximal tubule Na+,K+‐ATPase
Authors: IBARRA F. R. , CHENG S. X. JUN , AGRÉN M. , SVENSSON L.‐B. , AIZMAN O. , APERIA A. 
Published: March 2003

ABSTRACTThe natriuretic hormone dopamine and the antinatriuretic hormone noradrenaline, acting on α‐adrenergic receptors, have been shown to bidirectionally modulate the activity of renal tubular Na+,K+‐adenosine triphosphate (ATPase). Here we have examined whether intracellular sodium concentration influences the effects of these bidirectional forces on the state of phosphorylation of Na+,K+‐ATPase. Proximal tubules dissected from rat kidney were incubated with dopamine or the α‐adrenergic agonist, oxymetazoline, and transiently permeabilized in a medium where sodium concentration ranged between 5 and 70 mM. The variations of sodium concentration in the medium had a proportional effect on intracellular sodium. Dopamine and protein kinase C (PKC) phosphorylate the catalytic subunit of rat Na+,K+‐ATPase on the Ser23 residue. The level of PKC induced Na+,K+‐ATPase phosphorylation was determined using an antibody that only recognizes Na+,K+‐ATPase, which is not phosphorylated on its PKC site. Under basal conditions Na+,K+‐ATPase was predominantly in its phosphorylated state. When intracellular sodium was increased, Na+,K+‐ATPase was predominantly in its dephosphorylated state. Phosphorylation of Na+,K+‐ATPase by dopamine was most pronounced when intracellular sodium was high, and dephosphorylation by oxymetazoline was most pronounced when intracellular sodium was low. The oxymetazoline effect was mimicked by the calcium ionophore A23187. An inhibitor of the calcium‐dependent protein phosphatase, calcineurin, increased the state of Na+,K+‐ATPase phosphorylation. The results imply that phosphorylation of renal Na+,K+‐ATPase activity is modulated by the level of intracellular sodium and that this effect involves PKC and calcium signalling pathways. The findings may have implication for the regulation of salt excretion and sodium homeostasis.
Attenuation of the exercise‐induced increase in skeletal muscle Flt‐1 mRNA by nitric oxide synthase inhibition
Authors: GAVIN T. P. , WAGNER P. D. 
Published: March 2003

ABSTRACTWe investigated the vascular endothelial growth factor (VEGF) receptor [fms‐like‐tyrosine kinase (Flt‐1 and fetal liver kinase‐1 (Flk‐1)] response to acute exercise. In female Wistar rats, the VEGF receptor messenger RNA (mRNA) response to a single acute exercise bout was examined using semi‐quantitative Northern blot from the left gastrocnemius muscles at rest and post‐exercise at 0, 1, 2, 4, 8, 16, 24 and 48 h. Exercise altered both Flt‐1 and Flk‐1 mRNA, with significant increases in Flt‐1 mRNA at 1 and 24 h. However, post‐hoc analysis was unable to discern the time point where a significant increase in Flk‐1 mRNA occurred. To investigate the regulation of Flt‐1 mRNA by exercise we examined if nitric oxide synthase (NOS) inhibition alters the Flt‐1 mRNA response. Eight groups [Condition: Rest or Exercise; Drug: Saline, 30 mg kg–1Nω‐nitro‐L‐arginine methyl ester (L‐NAME), 300 mg kg–1L‐NAME or 300 mg kg–1D‐NAME] were used to determine the effect of NOS inhibition on the Flt‐1 mRNA response to exercise. L‐NAME, a known NOS inhibitor, attenuated the exercise‐induced increase in Flt‐1 mRNA by ∼50%. These findings suggest that: (1) exercise alters Flt‐1 and Flk‐1 gene expression; and (2) NO is important in the regulation of the Flt‐1 gene response to exercise.
Evidence that action potential generation is not the exclusive determinant to trigger spontaneous myogenic contraction of guinea‐pig urinary bladder smooth muscle
Authors: Imai T. , Tanaka Y. , Okamoto T. , Yamamoto Y. , Horinouchi T. , Tanaka H. , Koike K. , Shigenobu K. 
Published: March 2003

ABSTRACTUrinary bladder smooth muscle (UBSM) exhibits spontaneous contraction. This spontaneous mechanical activity is myogenic and can be closely related to the UBSM cell action potential to facilitate Ca2+ influx through voltage‐gated Ca2+ channels. In the present study, to know whether this membrane electrical event is the exclusive mechanism to trigger spontaneous smooth muscle contraction, we compared the inhibitory effects of Ca2+ channel blockers on the spontaneous action potential and mechanical activity in the isolated guinea‐pig UBSM. Both action potential and rhythmic contraction were generated spontaneously in the presence of atropine (1 µM), phentolamine (1 µM), propranolol (1 µM), suramin (10 µM) and tetrodotoxin (1 µM), which suggest that both phenomena were myogenic in origin. Nisoldipine (100 nM) and diltiazem (10 µM) completely eliminated the generation of action potential whereas its frequency was dramatically increased by a dihydropyridine Ca2+ agonist, BayK 8644 (1 µM). In contrast to disappearance of action potential in the presence of Ca2+ channel blockers, spontaneous contraction of UBSM was inhibited only partly by nisoldipine or diltiazem and most of the mechanical components persisted in these channel blockers. These results indicate that spontaneous action potential in UBSM cell is generated through the activation of L‐type voltage‐gated Ca2+ channels. The subsequent elevation of intracellular Ca2+ concentrations during a burst of action potentials can be partly responsible for the induction of UBSM mechanical activity. In addition, the present study provides evidence that UBSM spontaneous mechanical activity is also attributable to the mechanism(s) other than the generation of Ca2+ spike.
Nitric oxide modulates and adenosine mediates the tubuloglomerular feedback mechanism
Authors: Persson A. E. G. , Brown R. , Liu R. , Ollerstam A. 
Published: March 2003

ABSTRACTThe tubuloglomerular feedback (TGF) mechanism is an important regulator of the glomerular filtration rate (GFR) and urine excretion rate. It operates by sensing the distal delivery of fluid at the macula densa site and adjusting the tone of the glomerular arterioles to control GFR. We found evidence that nitric oxide is an important modulator of the setting of the sensitivity of the TGF mechanism. Studies on adenosine A1 receptor deficient mice have shown that these animals lack the TGF response and have an increased renin release. These findings show the important role of adenosine as a mediator of the signal for the TGF mechanism and as an inhibitor of renin release.
PGE1 induced transcapillary transport of 51Cr‐EDTA in rat skin measured by microdialysis
Authors: Iversen V. V. , Reed R. K. 
Published: March 2003

ABSTRACTInterstitial fluid pressure (Pif) is a key determinant in increasing the transcapillary driving pressure, pulling fluid from the microcirculation into the interstitial space at the onset of acute inflammatory reactions and the oedema formation associated with these. Prostaglandin E1 (PGE1) induces lowering of Pif in rat skin which increases transcapillary transport of 51Cr‐EDTA into the center of a tumor as measured by microdialysis. The aim of this study was twofold: First, to evaluate and develop the microdialysis technique thoroughly with regard to its suitability for investigating transcapillary water transport in rat skin using 51Cr‐EDTA as a tracer. Secondly, to evaluate the effect of PGE1 on transcapillary transport of 51Cr‐EDTA. This study demonstrates that PGE1 increases transcapillary transport of 51Cr‐EDTA into skin interstitium. There were no significant differences between the experimental probe and the control probe when calculations from the entire experiment (90 min) were compared. On the other hand, significant differences were observed by examining the experiment in smaller time intervals. PGE1 increased transcapillary transport of 51Cr‐EDTA during the first 15 min when administered through the microdialysis probe. This observation suggests that increased blood flow and/or permeability‐surface area product are responsible for raising the transcapillary transport of 51Cr‐EDTA, i.e. the transport is diffusion limited. Administration of PGE1 through the probe rather than around the probe resulted in less scatter between experiments than when PGE1 was injected subcutaneously around the probe.
Myosin remodelling in the contracting A7r5 smooth muscle cell
Authors: Fultz M. E. , Wright G. L. 
Published: March 2003

AbstractAim:  Using confocal microscopy and standard immunohistochemical techniques, changes in the structure of α‐actin and β‐actin as well as the distribution of myosin II were studied in the contracting A7r5 smooth muscle cell.Results:  Prior to stimulation, each of the three proteins were incorporated into filamentous structures extending the length of the cell body. At 30 min after stimulation by phorbol 12, 13 dibutyrate (PDBu), the system of densely packed β‐actin fibres was retained. By comparison, α‐actin and myosin were observed to undergo significant remodelling, characterized by loss in fibre structure and the formation of brightly fluorescing peripheral bodies. Co‐immunoprecipitation of α‐actin and myosin II suggested an association between the proteins. Consistent with this observation, dual immunostaining for α‐actin and myosin revealed strong co‐localization of the two proteins prior to stimulation. Following PDBu stimulation myosin II was observed to partially disassociate from α‐actin structure but showed significant co‐localization with α‐actin filaments and peripheral bodies throughout the interval of contraction. The use of cytochalasin B to block actin polymerization or the selective dissolution of α‐actin cable structure by thapsigargin produced similar patterns of change in α‐actin structure and the localization of myosin II.Conclusion:  The results support the concept of myosin liability and potential for remodelling. The results suggest that myosin undergoes extensive relocalization in association with α‐actin remodelling which may be an important determinant of contractile function in the A7r5 smooth muscle cell.
Blood flow distribution during elevated intraperitoneal pressure in the rat
Authors: Lindström P. , Källskog Ö. , Wadström J. , Persson A. E. G. 
Published: March 2003

AbstractAim:  Oliguria is seen during elevated intraperitoneal pressure, but the physiological mechanisms are not yet clarified. The purpose of the present study was to investigate the changes in renal function, cardiac output and distribution of systemic blood flow (BF) that occur in connection with an elevation of intra‐abdominal pressure (IAP) in a rat model by isotope‐labelled microsphere technique.Methods:  A 5 or 10 mmHg IAP was created by CO2 insufflation and maintained for 90 min in anaesthetized and mechanically ventilated rats. Rats with normal IAP served as controls. Blood flow and cardiac output measurements by injection of isotope‐labelled microspheres were conducted at three time points. Acid–base balance, urine output, glomerular filtration rate (GFR) and urinary excretion products were also followed.Results:  Glomerular filtration rate decreased [0.7–0.1 mL min−1 g−1 kidney weight (KW)] with elevated IAP, as did urine output (8.5–0.6 μL min−1 g−1 KW). Dramatic decreases were seen in renal excretion of sodium (by 97%), potassium (by 94%) and osmotic active substances (by 93%). Cardiac output was diminished by 54% at 5 mmHg and by 65% at 10 mmHg intraperitoneal pressure and systemic vascular resistance (SVR) was elevated threefold.Conclusion:  Cardiac output, measured by microsphere technique, decreased during elevated intraperitoneal pressure by CO2 in anaesthetized rats, while SVR was elevated and renal excretory functions were decreased to a large extent.
Sympathetic nerve activity in metabolic control – some basic concepts
Authors: Fagius J. 
Published: March 2003

AbstractA role for the sympathetic nervous system in hypertension has been looked for in relation to the ‘metabolic syndrome’ with associations between body weight, insulin sensitivity and hypertension. By use of microneurography human sympathetic responses to hypoglycaemia, normoglycaemic hyperinsulinaemia and food intake have been studied. A strong but differentiated influence of insulin‐induced hypoglycaemia comprises increase in muscle sympathetic nerve activity (MSNA) and the sudomotor part of skin sympathetic nerve activity (SSNA), whereas vasoconstrictor SSNA is inhibited. Responses to infusion of 2‐deoxy‐d‐glucose are identical, suggesting central nervous system glucopenia and not insulin to be the causative factor. Insulin infusion during normoglycaemia evokes a moderate increase in MSNA; SSNA and blood pressure does not change.After glucose ingestion MSNA displays a sustained increase, which is only partly elicited by insulin. A significant albeit weaker increase occurs after pure protein or fat meals, and after glucose ingestion in C‐peptide‐negative diabetic patients, with no insulin secretion. In healthy elderly people the MSNA response to food intake is weak, because of a high outflow already at rest; this is suggested to explain postprandial hypotension in the elderly, a paradoxical mechanism behind clinical autonomic failure.A pathophysiological role of MSNA in the metabolic syndrome with hypertension has been speculated. An association between obesity and elevated level of MSNA at rest is established; observed relationships to chronic insulin levels and hypertension are less unanimous. The adipous tissue regulating hormone leptin has become one focus of interest in ongoing attempts to elucidate a possible role of the human sympathetic nervous system in the ‘metabolic syndrome’ and hypertension.
Population dynamics of Mus minutoides and Steatomys pratensis (Muridae: Rodentia) in a subtropical grasslandin Swaziland
Authors: Monadjem A. 
Published: March 2003

SummaryThe population dynamics of Mus minutoides and Steatomys pratensis are virtually unknown. These two species were live‐trapped over a 12‐month period in a subtropical grassland in Swaziland. Numbers of M. minutoides were relatively high in winter, declined in spring and the population disappeared in summer and autumn. By contrast, numbers of S. pratensis increased gradually from winter to summer and reached a peak in autumn. There were no differences between the mean weights of male and female M. minutoides and S. pratensis. There were, however, seasonal differences in the mean weight of male S. pratensis, with highest weights recorded in summer. Individuals of both species came into breeding condition in spring (October–November). Reproduction had ceased by the end of autumn (April–May). Monthly survival rates of M. minutoides were highest in winter, but did not vary seasonally in S. pratensis. Burning had a pronounced effect on the distribution of S. pratensis. Steatomys pratensis individuals selected recently burnt but revegetated areas over unburnt areas. The effect of burning on the M. minutoides population is difficult to assess, as this species disappeared shortly after the fire.
A comparison of methods used to count the elephant population of the Addo Elephant National Park, South Africa
Authors: Whitehouse A. M. , Hall‐Martin A. J. , Knight M. H. 
Published: March 2003

AbstractEvaluation of alternative techniques used to estimate elephant population sizes is important in order to assess the accuracy of the results obtained, upon which management decisions may be based. Data from annual helicopter surveys carried out in the Addo Elephant National Park (1978–97) are compared with registration counts obtained from intensive ground surveys in which all elephants within the park are individually known. On average, total population size estimated in aerial surveys is 8.0% lower than registration counts (n1997 = 251), aerial calf (< 1 year) counts are 48.8% lower than registration counts, and aerial carcass counts are 50% below the total number of deaths documented in ground surveys. Registration counts provide more accurate demographic data than aerial surveys, the results of which are shown to vary widely and unpredictably, thus compromising their value. Where population estimates rely exclusively on aerial surveys, replicate counts are recommended in order to generate confidence intervals.
The elephant population of Samburu and Buffalo Springs National Reserves, Kenya
Authors: Wittemyer George 
Published: March 2003

AbstractA 21‐month individual identification project on the Samburu and Buffalo Springs National Reserves' elephant population was conducted between November 1997 and July 1999. The free ranging population, of at least 767 elephants, which relied heavily on areas outside the reserves, was individually identified. The numbers of elephants observed per day fluctuated but were greater during dry periods then wet. However, the sizes of aggregations were greater during wet periods. Preliminary investigation suggested that the population could be divided into two groups, which were designated resident and non‐resident family units. The groups comprised approximately equal numbers of cows and calves, but temporally had different reserve use patterns and calving peaks. The daily numbers of males and musth males were correlated with numbers of females. The reserves appeared to be a focal area for calving, indicating that the study area was of reproductive importance to the population. Demographic data indicated a female biased population sex ratio, with over twice the number of mature females to males. The observed sex skew was greatest for older age classes, and the density of musth bulls in the study area was low. The population was affected by poaching. Continued monitoring will assist conservation efforts by alerting authorities of major demographic or range use changes.
Effect of PPARγ ligands on the viability of gastric epithelial cells
Authors: Kojima K. , Shimada T. , Mitobe Y. , Yoshiura K. , Hiraishi H. , Terano A. 
Published: March 2003

Backgournd:Peroxisome proliferator‐activated receptors (PPAR) are a family of three nuclear receptors (PPARα, PPARδ, and PPARγ). Although recent evidence suggests a role for PPARγ in the regulation of colonic epithelial cell growth, the role for PPARγ in the stomach has not been established.Aim:To examine the expression of PPARγ and the effects of PPARγ ligands on the viability of gastric epithelial cells.Methods:MKN45 cells and primary cultured rat gastric epithelial cells were used. Troglitazone (TGZ) and 15‐deoxy‐Δ12, 14‐prostaglandin J2 (15d‐PGJ2) were used as PPARγ ligands. Expression of PPARγ was examined by RT–PCR and Western blot analysis. Cell viability was measured by WST‐1 assay and TUNEL assay was performed to detect apoptosis.Results:MKN45 cells expressed all subtypes of PPAR. PPARγ ligands decreased cell viability and induced cell death in a dose‐dependent manner, whereas ligands for PPARα and PPARδ had no significant effect. TUNEL assay showed that this cell death is apoptosis. Primary cultured rat gastric epithelial cells also expressed PPARγ and activation of PPARγ decreased cell viability.Conclusion:These results suggest that PPARγ plays an important role in the regulation of cell growth and cell death in gastric epithelial cells.
Treatment of mild to moderate ulcerative colitis and pouchitis
Authors: Gionchetti P. , Amadini C. , Rizzello F. , Venturi A. , Campieri M. 
Published: March 2003

SummaryThe meta‐analyses of published trials have shown topical therapy with 5‐aminosalicylic acid (5‐ASA) to be the treatment of choice in active distal ulcerative colitis. Oral aminosalicylates are effective for both distal and extensive ulcerative colitis, but in distal colitis the rates of improvement and remission are usually lower than those reported for rectal 5‐ASA therapy. An alternative to 5‐ASA therapy is represented by the new steroids; budesonide and beclometasone dipropionate (BDP) enemas, the most extensively studied, have been shown to be as effective as conventional steroids but with a significantly lower inhibition of plasma cortisol. Patients who do not respond to 5‐ASA or new steroids should be treated with oral steroids. Azathioprine or 6‐mercaptopurine may be effective in patients who do not respond or cannot be weaned off steroids. Treatment of pouchitis is largely empirical and few controlled studies have been carried‐out. Antibiotics are the treatment of choice and most patients make a good response to metronidazole or ciprofloxacin. Chronic refractory pouchitis may benefit from a prolonged course of a combination of antibiotics. Highly concentrated probiotics (VSL#3) are effective both for the prevention of pouchitis onset and the prevention of relapses.