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PubMed1996

In vitro immunopharmacologic effect of suramin on modifying Th-subset cytokine levels in splenocytes and T-cell clones: a therapeutic application for autoimmune disease.

The in vitro immunopharmacologic effect of suramin, a polysulfonated napthylurea, was examined on splenocytes and T helper (Th) 1 and 2 clones. Cytokine capture assays revealed that suramin inhibited the production of IFN-gamma, whilst IL-4 is increased in splenocytes. To examine whether suramin preferentially acts on Th cells, clones SP39A1 and SP41D5 were used. The former is a Th1 clone, whereas the latter is Th2. Suramin also inhibited IFN-gamma production by SP39A1, whilst IL-4 production by SP41D5 was enhanced. The action of suramin was of a dose-dependent nature. With regards to T cell proliferation, suramin inhibited the proliferation of both SP39A1 and SP41D5. The ability of suramin to manipulate Th subset cytokine balance can render it a feasible therapeutic agent in autoimmune disorders such as multiple sclerosis.

Animals↗
PubMed2005

Increased counteracting effect of eNOS and nNOS on an alpha1-adrenergic rise in total peripheral vascular resistance in spontaneous hypertensive rats.

OBJECTIVE: The hypertension in spontaneous hypertensive rats (SHR) may result from a hyperactive sympathetic nervous system or from insufficient bioactive nitric oxide (NO) due to increased oxidative stress. The present investigation aimed to elucidate the balance between these two systems by studying the ability of NO to oppose an adrenergic rise in total peripheral vascular resistance (TPVR). METHODS: In anesthetized, open-chest SHR and normotensive controls (WKY) on a respirator, blood pressure was recorded in the femoral artery and cardiac output measured by ascending aorta flow. Tyramine infusion (15 min, intravenously) was used to stimulate neuronal noradrenaline release. RESULTS: Tyramine induced an immediate but transient increase in TPVR, which was 4.5 times greater in SHR. After the non-selective NO synthase (NOS) inhibitor (L-NAME: N(omega)-nitro-L-arginine methyl ester), DeltaTPVRimm was 8.6 and 5.3 times increased in SHR and WKY, respectively, and TPVR remained elevated throughout the infusion period. Addition of alpha1-adrenoceptor antagonist (prazosin+L-NAME) abolished the TPVR response to tyramine. Neuronal NOS inhibitor (7-introindazole) increased DeltaTPVRimm only in SHR (2.1 times), and TPVR remained elevated. Inducible NOS inhibitor (1400W), free radical scavenger (tempol), NAD(P)H oxidase inhibitor (apocynin), angiotensin AT1 receptor antagonist (losartan), and ganglion blocker (hexamethonium) had no effect on the tyramine TPVR response in either strain. DeltaTPVR to hexamethonium, prazosin, and L-NAME were greater in SHR than WKY, and hexamethonium reduced DeltaTPVR to L-NAME in SHR only. CONCLUSIONS: The alpha1-adrenoceptor TPVR response to endogenous noradrenaline release was increased in SHR. This was not due to reduced bioavailable NO; on the contrary, NO counteraction was greatly increased, derived from endothelial NOS, with an additional role of neuronal NOS not seen in WKY. An influence of oxidative stress on these responses was not detected in either strain. In addition, a central eNOS sympathoinhibitory component appeared to influence baseline TPVR in SHR.

Adrenergic Uptake Inhibitors↗
PubMed2004

Flocculation of diatomite by methylated milk casein in seawater.

A new biodegradable flocculant was prepared from a common and inexpensive protein. Milk casein was methylated in a 0.05 M HCl methyl alcohol solution at room temperature. The methylated milk casein (MeCS), having a methylation degree of 81%, was applied to the separation or flocculation of diatomite in seawater (pH 8.1+/-0.1) at room temperature (18-23 degrees C). The flocculating ability of MeCS was evaluated by a sedimentation balance method (cumulative measurement method). The diatomite suspension was effectively flocculated by the addition of a small amount of MeCS (0.25 wt% of the diatomite weight). The results of sedimentation analysis showed that the size-frequency curve had a very sharp and high peak; thus the diatomite floc formed by MeCS had a rather uniform size. The settling velocity of diatomite floc at the appropriate MeCS dosages (0.25-2 wt% of diatomite) was about 3 x 10(-3) ms(-1).

Animals↗
PubMed2006

Effects of anthropogenic seawater acidification on acid-base balance in the sea urchin Psammechinus miliaris.

The purple-tipped sea urchin, Psammechinus miliaris, was exposed to artificially acidified seawater treatments (pH(w) 6.16, 6.63 or 7.44) over a period of 8 days. Urchin mortality of 100% was observed at pH(w) 6.16 after 7 days and coincided with a pronounced hypercapnia in the coelomic fluid producing an irrecoverable acidosis. Coelomic fluid acid-base measures showed that an accumulation of CO(2) and a significant reduction in pH occurred in all treatments compared with controls. Bicarbonate buffering was employed in each case, reducing the resultant acidosis, but compensation was incomplete even under moderate environmental hypercapnia. Significant test dissolution was inferred from observable increases in the Mg(2+) concentration of the coelomic fluid under all pH treatments. We show that a chronic reduction of surface water pH to below 7.5 would be severely detrimental to the acid-base balance of this predominantly intertidal species; despite its ability to tolerate fluctuations in pCO(2) and pH in the rock pool environment. The absence of respiratory pigment (or any substantial protein in the coelomic fluid), a poor capacity for ionic regulation and dependency on a magnesium calcite test, make echinoids particularly vulnerable to anthropogenic acidification. Geological sequestration leaks may result in dramatic localised pH reductions, e.g. pH 5.8. P. miliaris is intolerant of pH 6.16 seawater and significant mortality is seen at pH 6.63.

Acid-Base Equilibrium↗
PubMed2006

Urinary concentrating mechanism and Aquaporin-2 abundance in rats chronically treated with aluminum lactate.

The aim of this work was to study the effects of chronic administration of aluminum (Al) on the urinary concentrating and diluting mechanisms in the distal tubules and collecting ducts. Male Wistar rats were chronically treated with aluminum lactate for 12 weeks (0.575 mg Al/100g of body weight, i.p., three times per week). After 12 weeks, renal function of control and Al-treated rats was evaluated by clearance techniques. To study urinary concentrating mechanisms, renal function was also measured in control and Al-treated rats deprived of water, after the administration of desmopressin (vasopressin agonist) and after the infusion of hypertonic saline at increasing infusion rates. Sodium and water balance were impaired. We found decreased urinary concentrating ability in situations in which endogenous (thirst or infusion of hypertonic saline) or exogenous plasma antidiuretic hormone was increased. Solute-free water formation, measured during the infusion of hypotonic saline showed normal transport in the thick ascending limb. Aquaporin-2 (AQP2) expression was measured by Western blot to evaluate water permeability in collecting ducts. We found that Al produced downregulation of AQP2 in plasma membranes and intracellular vesicles, that could account for the impaired water handling. Administration of desmopressin increased AQP2 in plasma membranes, suggesting that Al did not impair trafficking of this protein, but could interfere with AQP2 synthesis.

Aluminum Compounds↗
PubMed2003

A duck hepatitis B virus strain with a knockout mutation in the putative X ORF shows similar infectivity and in vivo growth characteristics to wild-type virus.

Hepadnaviruses including human hepatitis B virus (HBV) and duck hepatitis B virus (DHBV) express X proteins, HBx and DHBx, respectively. Both HBx and DHBx are transcriptional activators and modulate cellular signaling in in vitro assays. To test whether the DHBx protein plays a role in virus infection, we compared the in vivo infectivity and growth characteristics of a DHBV3 strain with a stop codon in the X-like ORF (DHBV3-X-K.O.) to those of the wild-type DHBV3 strain. Here we report that the two strains showed no significant difference in (i). their ability to induce infection that resulted in stable viraemia measured by serum surface antigen (DHBsAg) and DHBV DNA, and detection of viral proteins and replicative DNA intermediates in the liver; (ii). the rate of spread of infection in liver and extrahepatic sites after low-dose virus inoculation; and (iii). the ability to produce transient or persistent infection under balanced age/dose conditions designed to detect small differences between the strains. Thus, none of the infection parameters assayed were detectably affected by the X-ORF knockout mutation, raising the question whether DHBx expression plays a physiological role during in vivo infection with wild-type DHBV.

Animals↗
PubMed2000

Perfusion and functional anatomy of the splenic remnant supplied by short gastric vessels.

BACKGROUND: Surgeons have described many methods to preserve the injured spleen for the maintenance of host defence. The volume and the perfusion of remaining splenic tissue are important for better functional results. Imaging the functioning tissue with radionuclide provides information about the physiology of the concerning organ. METHODS: Thirty rats were separated into three groups: control, explorative laparotomy alone; partial splenectomy, upper part of the spleen supplied by short gastric vessels was preserved after partial resection; and devascularized spleen, the entire spleen was preserved after ligation of splenic artery. The size, functional anatomy, and perfusion status of splenic tissue were assessed by liver-spleen scintigraphy using radiolabeled heat denatured red blood cells. RESULTS: In the partial splenectomy group, splenic radioactivity count, spleen/liver ratio, and radionuclide uptake were mildly reduced, and found to be 87% (P = 0.012), 91% (P = 0.16), and 88% (P <0.001) of the normal spleen, respectively. The area of functional tissue in the upper splenic remnant was 51% (P <0.001) of the normal spleen. In the devascularized spleen group, the radioactivity count, the ratio, and the uptake were 38% (P <10(-6)), 36% (P <10(-6)), and 49% (P <10(-6)) of the normal spleen respectively. The area of functional tissue in the devascularized spleen was calculated as 47% (P <10(-6)) of the normal spleen. CONCLUSIONS: The collateral circulation is insufficient for proper function of the entire spleen after disconnection of the main arterial blood supply. The functional tissue is markedly impaired. On the other hand, the upper part of the spleen is remained well perfused via the short gastric vessels. The collateral circulation is satisfactory for this splenic tissue after reduction of its volume. That size splenic tissue seems to have satisfactory functional ability. Proper functional results mostly depend on the balance between the volume and blood supply of the remaining splenic tissue.

Animals↗
PubMed2003

Career satisfaction and surgical practice patterns among female ophthalmologists.

PURPOSE: To identify gender differences in career satisfaction and practice patterns among Ontario ophthalmologists. METHODS: Survey mailed to all Ontario female ophthalmologists (n = 65) and a random sample of male ophthalmologists (n = 72). RESULTS: Men reported performing more operations per month (p = 0.039) and more operations in the last typical year (p = 0.003). More men than women were doing laser refractive surgery (p = 0.004). There were no gender differences in the proportion performing eye surgery or in the hours worked per week or weeks worked per year. Women reported being primarily responsible for their children for significantly more hours per week than men (p = 0.0003). There were no gender differences in any of the parameters of career satisfaction evaluated: number of hours worked, number of hours in the operating room (OR), balance with personal life, flexibility of work schedules, ability to structure work, relationship with colleagues and relationship with OR staff. INTERPRETATION: Despite spending significantly more hours as the primary supervisor of their children, female ophthalmologists were maintaining the same work week as their male colleagues and reported equal career satisfaction. Further investigation is needed to explore the differences between male and female ophthalmologists in the reported number of operations performed.

Child Care↗
PubMed2004

Screening for psychiatric disorders in patients with skin diseases: a performance study of the 12-item General Health Questionnaire.

OBJECTIVE: Although psychiatric disorders are frequent among dermatological patients, no study has formally assessed the performance of any psychiatric screening questionnaire in dermatological practice. This study tested the ability of the 12-item General Health Questionnaire (GHQ-12) to identify psychiatric morbidity in dermatological patients. METHODS: A sample of 521 adult inpatients (81% of all eligible patients) completed the GHQ-12 and were administered the Structured Clinical Interview for DSM-IV Axis I disorders (SCID-I) by a trained mental health professional masked to GHQ-12 score. RESULTS: The Receiver Operating Characteristic (ROC) analysis showed that GHQ-12 possesses substantial discriminatory ability (area under the curve=0.70). The best balance between sensitivity (68%) and specificity (64%) was found at the GHQ-12 cutoff score of 3/4. This threshold gave a likelihood ratio for a positive or negative result of 1.90 and 0.50, respectively. CONCLUSION: The performance of GHQ-12 was reasonably good for a self-administered questionnaire requiring only a few minutes to be completed and scored. Its routine use might increase recognition of psychiatric disorders in dermatological patients and contribute to improve patients' outcome.

Adult↗
PubMed1992

Gingivitis/stomatitis in cats.

Any alteration in the balance of bacterial challenge versus the host's ability to resist and repair will result in oral lesions that are similar in appearance. The bacterial cause of gingivitis and periodontitis in humans and in all other animals in which it has been studied is firmly established, and specific species of predominantly gram-negative anaerobes have been implicated. Naturally occurring or acquired immunopathologies are likely to result in premature dental disease. When oral disease is associated with the accumulation of plaque, a positive response can be achieved by reducing the bacterial challenge to the host through the maintenance of oral hygiene by timely professional dental prophylaxis and home care. Disease that is the result of atypical immune responses, however, can be much more difficult to manage. Such oral disease can occur with either immune deficiencies or exaggerated immune responses, and it is likely that multiple mechanisms are active concurrently. In any case, gram-negative anaerobes present in plaque are likely to be a major contributing factor. Therefore patients with chronic refractory gingivitis-stomatitis must be considered to be plaque intolerant. Only with a frequent regimen of aggressive and thorough professional dental treatment plus meticulous oral home care on a daily basis can one expect to keep these cases in remission. Because this is often unrealistic, the only other way to keep these patients free of disease is by total dental extraction. The tissues that are colonized by the causative organisms must be eliminated. All root tips and bony sequestra must be removed and healing with intact epithelium accomplished before these cases will go into remission. Edentulous feline patients that continue to have signs of gingivostomatitis have been found to have an area of nonhealed bony sequestrum and chronic osteomyelitis. Once effective debridement has been accomplished and epithelial healing completed, nonresponsive cases can be expected to go into remission (Color Plate 2, Figure 7). It is hoped that as more is learned about this frustrating problem, the many factors influencing feline oral disease will be scientifically documented. In the future, actual diagnoses can be systematically made early on in disease, and treatment will be more than just symptomatic.

Animals↗
PubMedDate not supplied

Evaluation and analysis of patient outcomes with an intrasegmental fixation system in lumbar spinal fusion.

BACKGROUND CONTEXT: A new spinal fixation system with polydirectional screws and modular links with interconnecting radial serrations has been developed. The system allows the linking of multiple points of fixation, two points at a time (intrasegmental fixation), thus eliminating the need for intraoperative contouring of rods or plates. PURPOSE: Evaluation of this new type of spine system was done through biomechanical studies, analysis of lumbar lordosis preservation postoperatively, and multicenter review of patient outcomes with a minimum of 1 year follow-up. STUDY DESIGN/SETTING: Biomechanical studies of the spine system were performed according to American Society for Testing and Materials (ASTM) standards. To evaluate the maintenance of lordosis, radiographs from the first 119 patients were reviewed by the authors. Analysis of patient outcomes consisted of a review of the first 259 patients who underwent spinal fusion surgery with the new spine system. PATIENT SAMPLE: Evaluation of patient outcomes consisted of 122 men and 137 women with an average age of 50+/-13 years (range, 22-96 years) and a mean follow-up of 20+/-6 months (range, 12-54 months). The patient population was at high risk for fusion failure, with 127 smokers (49%), 141 who had previous spine surgery (54%), 22 with osteoporosis (8%), 63 were obese (24%), and 32 with diabetes (12%). One hundred two patients (39%) had a one-level fusion, 105 patients (41%) had two levels fused, and 52 patients (20%) had three or more levels fused. The majority of patients (66%) were covered under workers' compensation. OUTCOME MEASURES/METHODS: Radiographic fusion was deemed successful when the presence of trabecular bridging bone from transverse process to transverse process was observed, as well as no fixation failure nor radiographic evidence of screw loosening. Clinical success was rated excellent, good, fair, or poor depending on the patients pain level, function, and pain medication intake. RESULTS: Biomechanical studies of this intrasegmental fixation system have shown it to be strong under both static and fatigue testing, with exceptional strength in compression bending. In evaluating preservation of lumbar lordosis, no statistically significant loss of lordosis was observed. Overall, radiographic fusion was noted in 229 of 259 patients (88%) and did not differ significantly (p>.10) by the number of levels fused. Clinically, 69 patients (27%) had an excellent result, 111 patients (43%) had a good result, 50 patients (19%) had a fair result, and 29 patients (11%) had a poor result. The high rate of successful patient outcomes did not differ significantly (p>.10) by the number of levels fused, or other patient or surgical variables, except for the satisfaction level of workers' compensation versus nonworkers' compensation. One hundred of 118 patients (85%) who were working before surgery returned to work at an average 9+/-4 months postoperatively (range, 2-20 months). The use of direct current (DC) stimulation in this population was reserved for patients with one or more risk factors for fusion failure and was noted to be of benefit. There were no recorded intraoperative complications, but postoperatively 5 device and 19 non-device-related complications (9%) were noted, which is comparable to other lumbar fusion series. CONCLUSIONS: The results of these analyses show consistent patient outcomes regardless of the number of levels fused with an intrasegmental system. This may be attributable to the increased biomechanical strength of the system at each segment, coupled with the ability of intrasegmental fixation to maintain sagittal plane balance through preservation of the patient's lordotic curve.

Adult↗
PubMed1996

Na+, K(+)-pump activity and skeletal muscle contractile deficits in the spontaneously hypertensive rat.

Skeletal muscles in an animal model of genetic hypertension (the spontaneously hypertensive rat. SHR) exhibit significant deficits in contractile performance. These deficits appear to be unrelated to the rise in blood pressure. Slow-twitch soleus muscles show a decrease in specific muscle tension and a reduced resistance to muscle fatigue during prolonged contractile activity. We tested the hypothesis that the reduced fatigue resistance occurs as a consequence of an impaired ability to maintain or restore Na+ and K+ balance across the sarcolemma during repeated contractions. This may result from a genetically based increase in the Na+ permeability of SHR muscles, coupled with a reduction Na+, K+ pump capacity as the animals mature. Soleus muscles in adult SHR exhibit a significant increase in intracellular Na+ content and a significant decrease in intracellular K+ content at rest. B6RB+ uptake in Na(+)-loaded hypertensive muscles is 45% less than predicted from the number of ouabain-binding sites available. Activation of Na+, K+ pumps using adrenaline or insulin produces a significantly smaller hyperpolarization in hypertensive soleus than in control muscles. Control soleus muscles are hyperpolarized for at least 10 min after a 4 min period of high-frequency activity, but hypertensive soleus muscles remain at resting polarity. Nonetheless, the number of ouabain-binding sites in hypertensive muscle is significantly greater than in control soleus, and binding affinities are similar. This apparent deficit in pump capacity might lead to a greater and more prolonged increase in extracellular K+ during repetitive contractions,and an associated decline in tension. Recently, we have been able to prevent the abnormal decrease in hypertensive soleus fatigue resistance by long-term treatment (8 weeks) with the Ca2+ blocker amlodipine. The therapy prevented or reversed the contractile deficits, but did not restore the responsiveness of the Na+, K+ pump to hormonal stimulation. The current data suggest that both a reduction in Na+, K(+)-pump capacity and changes in Ca2+ distribution play a role in the development of contractile deficits in hypertensive muscles.

Animals↗
PubMed1998

[Effects of a proprioceptive training program on sensorimotor capacities of the lower extremity in patients with anterior cruciate ligament instability].

Sensomotory function after ACL-reconstruction was tested prior and after a proprioceptive rehabilitation program with the Kinesthetic Ability Trainer (KAT 2000) which documented the static balance index (SBI). A control group consisting of healthy subjects was also tested two times with a time interval of six weeks. The results showed an adaptation effect to the testing device in the control group with an 17.12% increase of the SBI. There were no differences between the dominant and non dominant extremity. The active sensomotory function in the healthy knee of the operated patients showed no difference to the control group. Proprioceptive capabilities of the acl-reconstructed knee joints was significant reduced 6.42 weeks after surgery. A special proprioceptive rehabilitation program for six weeks significantly reduced this deficit. In the patient group sensomotory function of both knee joints could be increased to a level higher than in the control group. In the operated extremity the static balance index increased 27.75% and in the non injured extremity the SBI increased 16.88%.

Adult↗
PubMed2001

Mammalian play: training for the unexpected.

In this review, we present a new conceptual framework for the study of play behavior, a hitherto puzzling array of seemingly purposeless and unrelated behavioral elements that are recognizable as play throughout the mammalian lineage. Our major new functional hypothesis is that play enables animals to develop flexible kinematic and emotional responses to unexpected events in which they experience a sudden loss of control. Specifically, we propose that play functions to increase the versatility of movements used to recover from sudden shocks such as loss of balance and falling over, and to enhance the ability of animals to cope emotionally with unexpected stressful situations. To obtain this "training for the unexpected," we suggest that animals actively seek and create unexpected situations in play through self-handicapping; that is, deliberately relaxing control over their movements or actively putting themselves into disadvantageous positions and situations. Thus, play is comprised of sequences in which the players switch rapidly between well-controlled movements similar to those used in "serious" behavior and self-handicapping movements that result in temporary loss of control. We propose that this playful switching between in-control and out-of-control elements is cognitively demanding, setting phylogenetic and ontogenetic constraints on play, and is underlain by neuroendocrinological responses that produce a complex emotional state known as "having fun." Furthermore, we propose that play is often prompted by relatively novel or unpredictable stimuli, and is thus related to, although distinct from, exploration. We present 24 predictions that arise from our new theoretical framework, examining the extent to which they are supported by the existing empirical evidence and contrasting them with the predictions of four major alternative hypotheses about play. We argue that our "training for the unexpected" hypothesis can account for some previously puzzling kinematic, structural, motivational, emotional, cognitive, social, ontogenetic, and phylogenetic aspects of play. It may also account for a diversity of individual methods for coping with unexpected misfortunes.

Animals↗
PubMed2004

Antioxidants and physical performance in elderly persons: the Invecchiare in Chianti (InCHIANTI) study.

BACKGROUND: Muscle strength and physical performance in old age might be related to the oxidative damage caused by free radicals. OBJECTIVE: The objective was to assess the correlation of plasma concentrations and daily dietary intakes of antioxidants with skeletal muscle strength and physical performance in elderly persons. DESIGN: This study is part of the Invecchiare in Chianti (InCHIANTI) study, which was conducted in 986 Italians aged > or = 65 y. Physical performance was assessed on the basis of walking speed, ability to rise from a chair, and standing balance. Knee extension strength was assessed with a hand-held dynamometer. The European Prospective Investigation into Cancer and Nutrition (EPIC) questionnaire was used to evaluate the daily dietary intakes of vitamin C, vitamin E, beta-carotene, and retinol. Plasma alpha- and gamma-tocopherol concentrations were measured. Adjusted linear regression analyses were used to calculate regression coefficients per SD increase in plasma concentrations and daily dietary intakes. RESULTS: In adjusted analyses, plasma alpha-tocopherol was significantly correlated with knee extension (beta = 0.566, P = 0.003) and the summary physical performance score (beta = 0.044, P = 0.008). Plasma gamma-tocopherol was associated only with knee extension strength (beta = 0.327, P = 0.04). Of the daily dietary intake measures, vitamin C and beta-carotene were significantly correlated with knee extension strength, and vitamin C was significantly associated with physical performance (beta = 0.029, P = 0.04). CONCLUSIONS: Plasma antioxidant concentrations correlate positively with physical performance and strength. Higher dietary intakes of most antioxidants, especially vitamin C, appear to be associated with higher skeletal muscular strength in elderly persons.

Aged↗
PubMed1984

Metabolite changes in aged muscle during stimulation.

Metabolite concentrations of adenosine-5'-phosphate, phosphocreatine, and lactate were compared in adult and aged rat soleus and superficial, medial and deep, lateral gastrocnemius muscles after 3 min of moderate or intense stimulation in situ. The concentration of phosphocreatine in all muscles progressively decreased as contractile frequency increased. In most muscles, lactate increased coincident with greater contractile frequency. These changes were greater in aged muscles. Decreases in the concentration of adenosine-5'-phosphate with stimulation, where evident, were also greater in aged muscles. Metabolite levels in nonstimulated muscles were effected minimally by age. The cytochrome-c concentration was reduced with age in each muscle section. The results indicate that aged skeletal muscle has a lesser ability than adult skeletal muscle to maintain energy balance during contraction.

Adenosine Triphosphate↗
PubMed1993

Growth hormone attenuates Na(+)-dependent hepatic amino acid transport in endotoxemic rats.

The effects of human growth hormone (GH) on hepatic Na(+)-dependent amino acid transport were studied in endotoxin-treated rats. Adult rats received GH (6 mg/kg BW subQ q 12 hours x 4 doses) or vehicle prior to a single dose of Escherichia coli endotoxin (LPS, 7.5 mg/kg BW IP). Four hours after LPS administration, livers were excised and hepatocyte plasma membrane vesicles (HPMVs) were prepared by differential and Percoll density gradient centrifugation. Hepatocyte plasma membrane vesicle transport of [3H]-MeAIB, a highly selective system A substrate, [3H]-glutamine, a selective system N substrate, and [35S]-cysteine, a system ASC substrate, were measured by a rapid mixing/filtration technique. Vesicle purity and functionality were assessed by marker enzyme measurements and classic overshoots and timecourses that showed similar vesicle size. Endotoxin treatment resulted in a two-fold increase in the activities of systems N and ASC, which was the result of an increase in carrier Vmax (Km was unchanged), and a four-fold stimulation of system A. Pre-treatment with GH diminished the endotoxin-induced increase in Na(+)-dependent amino acid transport by 60%-80%; this reduction in carrier-mediated transport activity was a result of a decrease in Vmax, consistent with a decrease in the number of functional transporter proteins in the plasma membrane. Growth hormone treatment attenuates the endotoxin-induced increase in the activities of the major Na(+)-dependent transporters in rat liver. This may diminish hepatic ureagenesis and spare amino acids for peripheral protein synthesis and thereby explain, at least in part, the ability of growth hormone to promote positive nitrogen balance in catabolic states.

Amino Acids↗