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PubMedDate not supplied

Study of HLA class I restriction and the directed antigens of cytotoxic T lymphocytes at the tumor sites of ovarian cancer.

The molecular basis of T-cell-mediated recognition of ovarian cancer cells remains to be fully addressed. In this study we investigated HLA class I restriction and directed antigens of cytotoxic T lymphocytes (CTL) at the sites of ovarian cancer. Three HLA-class-I-restricted CTL lines were established from the tumor sites of ovarian cancer by culturing tumor-infiltrating lymphocytes or tumor-associated ascitic lymphocytes with interleukin-2: (1) HLA-A2402-restricted and ovarian-adenocarcinoma-specific CTL, (2) HLA-A2-restricted CTL recognizing histologically different cancers, and (3) HLA-B52-restricted and ovarian-cancer-specific CTL. HLA-A0201, HLA-A0206 and HLA-A0207 tumor cells were lysed by the HLA-A2-restricted CTL. HLA-B52 restriction of the third CTL line was confirmed by the transfection of HLA-B5201 cDNA into the tumor cells. The HLA-A2-restricted CTL recognized the SART-1, but not the MAGE-1 or MAGE-3 antigen. These results may facilitate a better understanding of the molecular basis of tumor-specific immunity at the tumor site of ovarian cancer.

Animals↗

PubMed2006

Cervical spine segmental vertebral motion in healthy volunteers feigning restriction of neck flexion and extension.

The purpose of this study was to obtain comparative data concerning the percentage contribution of segmental cervical vertebral motion to the cervical range of motion (ROM) in healthy volunteers under two conditions: (1) normal, voluntary neck flexion and extension and (2) feigned restriction of neck flexion and extension. Each healthy subject's angular motion over forward cervical flexion and extension was measured first by X-ray analysis during normal, voluntary motion. Then the subjects were asked to pretend that they had a 50% restricted neck range due to pain or stiffness and thus to move in both flexion and extension only as far as about 50% of their normal range. A total of 26 healthy subjects (ten males and sixteen females, age 28.7+/-7.7 years) participated. The total angular motion from C2 to C7 was normal in the unrestricted condition and was significantly reduced in the feigned restriction condition (p<0.001). The percentage contribution of each of the functional units C2-C3 to C6-C7 to this rotation was different between the normal unrestricted and the feigned restricted conditions. In the feigned restricted neck flexion and extension, a shift occurred in the pattern of how each segment contributes to the total angular range. A greater percentage contribution was made by C2-C3 and C3-C4 than under normal conditions (P<0.01), and the percentage contribution to total rotation made by C6-C7 became much less under the feigned restricted movements than under normal, unrestricted neck range (p<0.001). Thus, simulated or feigned restricted neck ROM affects the percentage contribution of the functional units C2-C3 to C6-C7 by showing a higher percentage contribution of the upper cervical segments and less contribution to the angular rotation by the lowest cervical segment. Feigners of restricted neck range thus produce a pattern different from nonfeigning subjects.

Adult↗

PubMed1985

Adaptation of middle aged rats to long-term restriction of dietary vitamin D and calcium.

Previous studies have shown that middle aged rats do not increase renal 1,25-dihydroxyvitamin D3(1,25(OH)2D3) production in response to short-term (4 weeks) dietary vitamin D and calcium restriction. The purpose of the experiments reported here was to determine if middle aged rats demonstrate adaptation to long-term restriction of dietary calcium and vitamin D and to compare that adaptation to the adaptation seen in young rats. Middle aged (14-16 months) Fischer 344 rats were fed either a 0.02% calcium, vitamin D-deficient (restricted) or a 1.2% calcium, vitamin D-replete (control) diet. Rats from each group were sacrificed after 1.5, 3.0, 4.5, and 6.0 months on the diets. Renal conversion of 25(OH)D3 to 1,25(OH)2D3 and 24,25(OH)2D3 was measured in vitro using isolated renal cortical slices. Renal 1,25(OH)2D3 production in the restricted group was not significantly increased until 3 months and reached a maximum of 85% higher than the control at 4.5 months. Renal 24,25(OH)2D3 production was significantly decreased after only 1.5 months of restriction and was decreased maximally by 70% at 3.0 months. Serum calcium remained in the range 11-12 mg/100 ml in both diet groups, and serum immunoreactive PTH (iPTH) was modestly increased one- to twofold in the restricted group compared to the control group. In contrast, young rats (3 months old) fed the deficient diet for 1 month had a fourfold increase in renal 1,25(OH)2D3 production and a 71% decrease in 24,25(OH)2D3 production. Feeding the deficient diet also produced a 43% reduction in serum calcium and a 13-fold increase in serum iPTH. These findings demonstrate that middle aged rats do alter their 25(OH)D metabolism in response to long-term vitamin D and calcium restriction. However, both the rapidity and the magnitude of the response is decreased compared to that seen in the young rat. This blunted vitamin D response in the middle aged rat reflects the lack of a decrease in serum calcium and the marginal increase in serum iPTH in response to vitamin D and calcium restriction.

Aging↗

PubMed1992

Effect of food restriction on the phosphocreatine energy shuttle components in rat heart.

Malnutrition has been associated with changes in cardiac metabolism and performance. We have previously reported a diabetic-type cardiomyopathy associated with chronic food restriction and weight loss. Because the creatine-phosphocreatine-creatine kinase system is important in the contractile process, we studied the components of this system in rats fed a food-restricted diet (33% of control animal intake). After 4 weeks of food restriction, total creatine kinase (CK) activities were reduced by 28% in ventricles and by 38% in atria. The CK isoenzymes in the heart were not equally affected. The BB isoenzyme was decreased by 77% and 78%, the MB isoenzyme by 45% and 43%, the MM isoenzyme by 22% and 19% and CKmito by 16% and 15% in ventricles and atria, respectively. In contrast, brain CK activity which is predominantly the BB isoenzyme, was slightly higher in the food-restricted than in control rats. Further studies on ventricular tissue from food-restricted rats revealed a 27% decline in myofibrillar CR activity and a 58% decline in myofibrillar ATPase activity. Phosphocreatine and creatine concentrations were not changed by food restriction, however, ATP was decreased by 23% in ventricles from rats on the restricted diet. Cardiac mitochondrial oxidative phosphorylation was also impaired. State 3 respiration with alpha-ketoglutarate was reduced 20% in the food-restricted heart. These changes are compared to those which we previously observed in the diabetic rat heart and the significance of these findings is discussed.

Adenosine Triphosphatases↗

PubMed1996

Change in fetal urine production rate in growth-restricted fetuses after maternal meal ingestion.

OBJECTIVE: To determine if fetal urine production is affected by maternal meal ingestion in growth-restricted fetuses. METHODS: We studied 25 normal-growth fetuses in uncomplicated pregnancies and 15 growth-restricted fetuses, all after 30 weeks' gestation. Serial fetal bladder volume measurements were obtained at 2-3 minute intervals with ultrasonography 2 hours before and 2 hours after maternal breakfast. The hourly fetal urine production rate in each maternal state was calculated from the bladder volume measurements. The amniotic fluid index (AFI) and the pulsatility index of both umbilical and fetal middle cerebral arteries were also measured. RESULTS: Two of the 15 growth-restricted fetuses were excluded from analysis, one because it was anomalous and the other because it was not small for gestational age at birth. In the normal-growth fetuses, the hourly fetal urine production rate increased significantly after maternal breakfast (mean +/- standard deviation 30.2 +/- 11.7 versus 41.1 +/- 14.6 mL/hour, P < .001). In contrast, in the growth-restricted fetuses, the rate did not change after maternal breakfast (24.6 +/- 6.2 versus 24.9 +/- 5.7 mL/hour). Although the urine production rate before breakfast did not differ between groups, 2 hours after maternal breakfast it was significantly lower in the growth-restricted fetuses than in the control group (normal-growth) (P < .001). The AFI also was significantly lower in the growth-restricted fetuses than in the control group (15.0 +/- 3.5 versus 18.6 +/- 5.0 cm, P < .04). There were no significant differences in the pulsed Doppler studies. CONCLUSION: In contrast to normal-growth fetuses, maternal meal ingestion for growth-restricted fetuses does not increase fetal urine production. Decreased fetal urine production in the maternal fed state may lead to decreased amniotic fluid volume in growth-restricted fetuses without obvious hypoxia.

Amniotic Fluid↗

PubMed1989

Effect of chronic caloric restriction on physiological variables related to energy metabolism in the male Fischer 344 rat.

In the present study, a number of physiological and behavioral measures that are related to metabolism were continuously monitored in 19-month-old male Fischer 344 rats that were fed ad libitum or fed a caloric restricted diet. Caloric restricted rats ate fewer meals but consumed more food during each meal and spent more time eating per meal than did rats fed ad libitum. Therefore, the timing and duration of meals as well as the total number of calories consumed may be associated with life extension. Average body temperature per day was significantly lower in restricted rats but body temperature range per day and motor activity were higher in restricted rats. Dramatic changes in respiratory quotient, indicating rapid changes in metabolic pathway and lower temperature, occurred in caloric restricted rats when carbohydrate reserves were depleted. Lower body temperature and metabolism during this time interval may result in less DNA damage, thereby increasing the survival potential of restricted rats. Nighttime feeding was found to synchronize physiological performance between ad libitum and caloric restricted rats better than daytime feeding, thereby allowing investigators to distinguish the effects of caloric restriction from those related solely to the time-of-day of feeding.

Animals↗

PubMed1989

Effect of chronic caloric restriction on hepatic enzymes of intermediary metabolism in the male Fischer 344 rat.

It is well established that caloric restriction extends life span and significantly retards the rate of occurrence of most age-associated degenerative disease processes. A paucity of data exists relative to the mechanisms by which caloric restriction accomplishes these events. We have examined the effect of caloric restriction in rats on several hepatic enzymes of intermediary metabolism. The activities of glycolytic and supporting enzymes including lactate dehydrogenase, pyruvate kinase, sorbitol dehydrogenase, and alcohol dehydrogenase were all decreased in response to caloric restriction. Fructose 1-phosphate aldolase and creatine phosphokinase were not altered. Likewise, enzymes associated with lipid metabolism (malic enzyme and glycerokinase) were reduced (fatty acid synthetase was reduced, but not to a statistically significant degree). Activities of enzymes supporting gluconeogenesis (glutamate oxaloacetate transaminase, tyrosine aminotransferase, glutamate pyruvate transaminase, glutamate dehydrogenase, amino acid oxidase, malate dehydrogenase, and glucose 6-phosphatase) were either unchanged or increased significantly by caloric restriction. Glucagon levels were decreased. Comparisons between young ad libitum fed and older calorically restricted rats revealed similar but not identical metabolic activity. These results suggest that caloric restriction produces an effect on intermediary metabolism, favoring the role of glucagon and glucose synthesis; but limiting the role of insulin and glucose catabolism in the liver. The former observation provides for the efficient support of peripheral tissues and the latter a level of energy production necessary only for self maintenance. Limited lipid metabolism suggests decreased potential for fatty acid epoxide formation and free radical damage to cellular macromolecules. Additionally, caloric restriction may delay the progressive age associated changes in the activities of some of the enzymes investigated.

Age Factors↗

PubMed1995

The effect of neonatal pinealectomy on the inhibitory actions of food restriction on vaginal opening and collagen aging in the rat.

Long-term food restriction is known to inhibit development and aging in the rat. These actions may be mediated by the pineal hormone, melatonin, whose secretion is increased by food restriction. This mechanism was investigated by studying the effects of pinealectomy in ad libitum fed and food restricted rats of both sexes living under normal conditions of temperature (23 degrees C) and lighting 12 h light:12 h dark cycle) over a period of 400 days. Pinealectomies were performed at the age of 5 days. Pinealectomy did not affect the amount of food eaten per day. Vaginal opening occurred at age 35 days in ad libitum fed female rats and was delayed to 49 days (P < 0.001) in rats whose food intake was restricted by 35%, but only to 41 days (P < 0.001) if food restricted (FR) rats were pinealectomized (Px). The inhibitory effect of food restriction on body growth and tail tendon collagen fibre aging was the same in both intact and pinealectomized rats. At the conclusion of the study in middle age at 400 days, plasma melatonin levels 4 h into the dark cycle were higher in food restricted than in ad libitum fed rats (P = 0.015). This study provides evidence for a role of the pineal in mediating the inhibitory action of food restriction on vaginal opening, but not on body growth or collagen aging in tail tendon up to middle age.

Aging↗

PubMed1991

The relationship between MHC restricted and allospecific T cell recognition.

The existence in the mature T cell repertoire of a high precursor frequency of cells which recognise allogeneic MHC molecules appears to contradict the well-established dogma of positive selection for self MHC restriction. In order to explore the possibility that alloreactive cells are derived from a fraction of the repertoire that is not self-MHC-restricted, the contribution of in vivo-primed T cells to "primary" alloresponses was investigated. Peripheral blood T cells were separated into virgin and memory populations by sorting for low and high levels of LFA-3 expression, and their proliferative responses to MHC incompatible stimulator cells was quantitated. The results demonstrated that approximately half of a "primary" alloresponse is contributed by previously primed T cells that, by definition, must be self-MHC restricted. Furthermore it was possible to define the original MHC-restricted antigen specificity of two T cell clones raised against the allospecific HLA-DR1 from a DR4Dw4/DRw13DW19 responder. The emerging consensus view that anti-MHC alloreactive T cells, like antigen-specific T cells, are specific for MHC/peptide complexes, and have a parental self-MHC restriction, begs a structural explanation. Comparison of multiple DR beta 1 domain sequences reveals that DR molecules fall into groups that have extensive homology in the residues on the beta 1 domain alpha-helix that are predicted to point up towards the T cell receptor (histotopic), and thus to determine MHC restriction. Given that the DR alpha chain is invariant this creates the possibility that anti-DR allorecognition can mimic self-restricted recognition. Within these groups of histotopically similar DR products there are multiple differences in the peptide-binding residues that lie on the inner aspects of the alpha-helix or on the floor of the antigen-binding groove. As a consequence, it is predicted that a different array of endogenous peptides will be bound, due to determinant selection. Thus, allorecognition within these groups may result from the recognition of endogenous peptides that are bound by stimulator but not by responder MHC products, seen in a self-restricted manner. In combinations where histotopic similarity does not exist, allorecognition may be best explained by the chance occurrence of a receptor selected for intermediate affinity for thymically expressed MHC molecules having a higher affinity for an allogeneic histotope. Such a receptor would have been deleted in a thymus expressing the allospecificity, but would be perceived as "safe" in the absence of this MHC product.

Antigen-Antibody Reactions↗

PubMed1991

Effects of maternal calorie-restricted diet on development of the foetal heart, as evaluated in primary cultures of rat myocardial cells.

Very-low-calorie diets have been implicated in causing ventricular arrhythmias and sudden cardiac death. Furthermore, studies indicate that maternal carbohydrate-restricted diets consumed during pregnancy and lactation reduce foetal growth, parturition and postnatal survival of rat pups. In this study, Sprague-Dawley rats were maintained on a semi-purified full-calorie or 50% carbohydrate-calorie-restricted diet throughout pregnancy. The function and integrity of myocardial cell cultures obtained from 3-5-day-old offspring from both groups of dams were evaluated after a drug-induced toxic challenge. After the myocytes had been in culture for 4 days, they were exposed to various concentrations of amitriptyline (1 x 10(-3) to 1 x 10(-5) M). Morphology, beating activity, lactate dehydrogenase release, glucose utilization, beta-adrenergic receptor [125I]iodopindolol binding, and cellular adenosine triphosphate content were evaluated for 24 hr after drug exposure. There were no significant differences in morphology, beating activity or glucose utilization between the full-calorie and calorie-restricted groups. When compared with the full-calorie group, lactate dehydrogenase release from the calorie-restricted group was significantly lower at 8 hr for the untreated controls and those cells exposed to 1 x 10(-4) and 1 x 10(-5) M-amitriptyline. Adenosine triphosphate levels were lower in untreated controls from the calorie-restricted group when compared with the full-calorie group at 4 hr. Within the calorie-restricted group, those cultures exposed to 1 x 10(-4) M-amitriptyline had significantly depressed adenosine triphosphate levels after 8 hr of drug treatment when compared with their respective untreated controls. Finally, the calorie-restricted group had significantly increased binding affinities of beta-receptors. Thus, maternal consumption of calorie-restricted diets during pregnancy may affect the myocardial functional capacity and integrity of the offspring.

Adenosine Triphosphate↗

PubMed1993

Selected immune responses of adult cotton rats (Sigmodon hispidus) to dietary restriction.

1. We examined the influence of moderate to severe dietary restriction on immune system function in adult cotton rats. Animals (N = 80) were fed ad lib. (controls) or restricted [moderate = 80% ad lib. for 1 or 2 weeks; severe = 80% ad lib. for 1 or 2 weeks followed by 40% ad lib. for one (week 3) or two (week 4) additional weeks] amounts of food for 1-4 weeks. 2. Average body weight loss for severely restricted animals in week 4 was 17%; dietary treatments had no measurable effect on hematological parameters (hematocrit, white blood cell count), lymphoid organ weights (thymus gland, spleen, popliteal lymph nodes), and mononuclear cell yields from lymphoid organs. 3. Cell-mediated immune function was assessed in vitro by a lymphoproliferative response assay and in vivo by a delayed-type hypersensitivity response assay. 4. Proliferative responses of spleen cell cultures stimulated with concanavalin A (Con A, Canavalia ensiformis) and pokeweed (PWM, Phytolacca americana) were normal or significantly greater among moderately restricted than control cotton rats during week 1 and week 2. 5. Lymphoproliferative responses of severely restricted animals were normal or reduced during week 3 and week 4. 6. Delayed-type hypersensitivity responses to the contact antigen oxazolone were significantly depressed among severely restricted animals in week 4 compared to controls. 7. In comparison with laboratory rodent strains, our initial results indicate that immune system function in adult cotton rats is not as sensitive to short term (1-4 weeks) periods of dietary restriction. 8. Immune system function was related to changes in body weight as a result of feed restriction.

Animals↗

PubMedDate not supplied

Caloric and carbohydrate restriction in the kidney: effects on free radical metabolism.

Carbohydrate restriction and caloric restriction (60% restriction of calories in relation to controls in both cases) were imposed on OF1 mice during 8 weeks in their growing phase. The three groups of animals ingested the same amount of vitamins and minerals. Kidney ascorbate strongly decreased in both restriction groups. Nevertheless, global caloric restriction significantly increased kidney antioxidant glutathione (GSH)/oxidized glutathione (GSSG) ratio, a sign of a reduced kidney oxidative stress. Increased glutathione peroxidase and cytochrome oxidase activities and decreased in vivo peroxidation were found in the kidney when the restriction was performed by substituting carbohydrates by nonnutritive bulk. No significant changes were observed for superoxide dismutase, catalase, glutathione reductase, glutathione, uric acid, malondialdehyde (HPLC), or in vitro sensitivity to peroxidation in the kidney. The results, reported for the first time in this tissue, show that short-term caloric restriction can increase the capacity for enzymatic decomposition of hydroperoxides and can decrease oxidative stress in the kidney, thus suggesting a role for free radical metabolism in the caloric restriction phenomenon.

Animals↗

PubMed1993

Effect of feed restriction on serum somatotropin, insulin-like growth factor-I-(IGF-I) and IGF binding proteins in cyclic heifers actively immunized against growth hormone releasing factor.

Feed restriction often increases serum somatotropin (ST) and decreases insulin-like growth factor-I (IGF-I) in ruminants; however, the mechanisms responsible for this change in ST and IGF-I are not well defined. We investigated the effects of feed restriction on serum ST, IGF-I, IGF binding proteins (IGFBP), insulin and nonesterified fatty acids (NEFA) in cyclic Angus and Charolais heifers (n = 15) previously immunized against growth hormone releasing factor (GRFi) or human serum albumin (HSAi). Cows were fed a concentrate diet ad libitum (AL) or were restricted to 2 kg cotton seed hulls (R) for 4 d. Each heifer received each dietary treatment in a single reversal design. As anticipated, GRFi decreased ST, IGF-I and insulin (P < .05). In addition, GRFi decreased serum IGFBP-3 (P < .01), but increased IGFBP-2 (P < .01). Feed restriction resulted in an increase in serum ST in HSAi, but not in GRFi heifers. Regardless of immunization treatment, feed restriction decreased serum IGF-I and insulin, and increased NEFA (P < .01). In conclusion, the increase in serum ST levels observed during feed restriction was blocked by active immunization against GRF. However, feed restriction resulted in decreased serum IGF-I in GRFi heifers in spite of initial low levels of IGF-I (due to GRFi). Although GRFi decreased levels of IGFBP-3 and increased levels of IGFBP-2, feed restriction for 4 d did not alter serum IGFBP.

Animals↗

PubMed2004

Simultaneous measurements of umbilical venous, fetal hepatic, and ductus venosus blood flow in growth-restricted human fetuses.

OBJECTIVE: The purpose of this study was to evaluate the changes in the distribution of the umbilical venous blood flow to the liver and to the ductus venosus in intrauterine growth-restricted human fetuses in relationship with dilation of the ductal isthmic diameter. STUDY DESIGN: Umbilical venous flow, ductus venosus blood flow, and blood flow to the fetal liver were measured in 56 severely intrauterine growth-restricted fetuses with an abnormal pulsatility index of the umbilical artery and were compared with 137 normal control fetuses. Percentages of umbilical venous blood flow through the ductus venosus and to the fetal hepatic lobes were calculated. Z-scores for control fetuses and intrauterine growth-restricted fetuses were constructed by the evaluation of the inverted smoothed percentiles. The distributions of the Z-scores was compared with a 1-sample t-test. RESULTS: The ductus venosus blood flow that was corrected for fetal weight was increased significantly in intrauterine growth-restricted fetuses compared with control fetuses (P=0); the median values (interquartile range) for comparable ages of gestation was 41.3 mL/min/kg (range, 26.2-64.0 mL/min/kg) and 30.8 mL/min/kg (range, 19.9-42.8 mL/min/kg), respectively. As a consequence, ductus venosus shunting was increased in intrauterine growth-restricted fetuses compared with control fetuses (P =0). In 23 of 30 intrauterine growth-restricted fetuses, the percentage of umbilical blood flow that was shunted through the ductus was>90th percentile of control fetuses. Ductal diameters were significantly greater in growth-restricted fetuses than in control fetuses (P =.0001). The percentage of blood flow to the right lobe showed a significant reduction (P =.0223), with evidence of reversed blood flow from the right lobe and portal system into the ductus venosus that was provided both by volume blood flow calculations and by direct pulsed Doppler waveform direction. CONCLUSION: In severe intrauterine growth-restricted fetuses, Doppler examination of blood flow volume proved a significant increase in the shunting of umbilical vein blood flow through the ductus venosus that was associated with the dilation of the ductal isthmic diameter. These changes provide a relatively constant blood flow to the heart and brain at the expense of fetal hepatic perfusion.

Adult↗

PubMed2004

Reduction of anxiety after restricted feeding in the rat: implication for eating disorders.

BACKGROUND: Eating-disorder patients exhibit not only abnormal eating attitudes but also pathologic anxiety-like behaviors. The specific nature of the relationship between dieting and anxiety-like behavior is unknown. METHODS: To investigate the adaptational changes that resulted from chronic restricted scheduled feeding (2-hour access per day for 2 weeks) and subsequent free refeeding, longitudinal changes in the microstructure of feeding behavior were studied in male rats. To study the relationship between restricted feeding and anxiety-like behavior, separate rats were tested in the elevated plus-maze under the following conditions: 1) free feeding; 2) acute food restriction (2-hour access for 1 day); 3) chronic food restriction (for 10 days); or 4) postrecovery (after 10 days of free feeding subsequent to chronic food restriction). RESULTS: The effects of chronic food restriction on meal structure diminished within a few days after refeeding. Decreased anxiety-like behavior was seen during acute and chronic food restriction and did not reflect nonspecific behavioral activation. Anxiolytic-like effects persisted after 10 days of refeeding. CONCLUSIONS: Chronic food restriction produced reductions in anxiety-like behavior that persisted beyond the normalization of food intake patterns. The findings might have etiologic and pathophysiologic relevance for the restrained eating pattern in eating-disorder patients with comorbid anxious symptoms.

Adaptation, Psychological↗

PubMed2005

Restrictive left atrial outflow adversely affects outcome after the modified Norwood procedure.

OBJECTIVE: Moderate restrictive foramen ovale in neonates with hypoplastic left heart syndrome (HLHS) is considered to be favourable, reducing pulmonary overcirculation, before modified Norwood operation. However, some newborns with severe restriction of interatrial communication will have pulmonary vascular disease at birth, which correlates with increased perioperative mortality. This article studies the post-Norwood hemodynamic patterns and outcome for the particular group of HLHS newborns with restrictive left atrial outflow compared to other patients. METHODS: Restrictive left atrial outflow is defined as mitral and/or aortic atresia with intact ventricular septum, and restrictive foramen ovale, with 3 mm diameter or less with mean interatrial pressure gradient more than 5 mmHg at preoperative echo-Doppler. Four neonates fulfilled these criteriae among 18 consecutive patients, who underwent Norwood procedure from October 2002 to December 2003. Mean arterial pressure, heart rate, mean common atrial pressure, urinary output, central venous and arterial oximetry data, serum lactate levels, and dosages of milrinone, phentolamine and norepinephrine were collected at 0, 6, 12, 18 and 24 h after operation. Data were summarized as mean+/-SEM. For univariate comparison of different variables, Student's t-test was used. RESULTS: The postoperative hemodynamic pattern of patients with restrictive left atrial outflow was characterized by hypoxemia and low cardiac output. Arterial (66+/-3.0% vs 76+/-1.0%, P=0.01) and central venous (37+/-1.2 vs 52+/-1.1%, P=0.001) oxygen saturations were much lower than in patients without restriction. Arterio-venous oxygen saturation difference was wider (29+/-2.4% vs 23+/-0.9%, P=0.02) and serum lactate levels were higher (10.8+/-3.0 vs 2.8+/-0.2 mmol/l, P=0.03). Common atrial pressures were more elevated (12+/-0.8 vs 8+/-0.3 mmHg, P<0.001) and higher norepinephrine doses were needed (0.44+/-0.15 vs 0.06+/-0.01 microg/kg/min, P=0.03). The difference for the mean arterial pressures did not reach the significance level (48+/-2.0 vs 51+/-2.0 mmHg, P=0.2). Operative mortality was higher 75% (3/4) compared to 14.3% (2/14, P=0.04) for the other patients. CONCLUSIONS: Restrictive left atrial outflow adversely affects outcome after modified Norwood procedure. Abnormal pulmonary vasculature leading to insufficient pulmonary perfusion is incriminated. To improve outcome, implantation of larger size modified Blalock-Taussig or right ventricle-to-pulmonary artery shunts and routine use of postoperative mechanical assist device should be considered.

Aortic Valve↗

PubMed2006

Effect of nutrient restriction on the somatotropes and substance P-immunoreactive cells in the pituitary of the female ovine fetus.

The maternal environment affects fetal development and may influence the physiology of the adult. Fetal growth hormone (GH) is increased by maternal undernutrition but the mechanisms responsible are unknown. This study determined the effect of maternal undernutrition on the development of fetal pituitary somatotropes in the female. Ewes were grouped randomly into control (fed 100% of requirements) or nutrient restricted (fed 50%) from Days 28 to 78 of gestation. At Day 78, the ewes were killed and fetuses collected (Day 78 NR (nutrient restricted): n=6; Day 78C (control): n=6). Remaining ewes were realimented to 100% of nutritional requirements and were killed at Day 135 (Day 135 NR (nutrient restricted): n=6; Day 135 C (control): n=6). Somatotropes were visualized immunocytochemically and the size, mean density, total percentage and proportion colocalized with substance P were determined for each group. Nutrient restriction increased (p<0.01) the density of pituitary cells in Day 78 fetuses but this difference was no longer apparent by Day 135 after realimentation. The density and proportion of somatotropes were not different between treatment groups at Day 78 but were significantly (p<0.05) lower in the nutrient restricted Day 135 fetuses as compared to the Day 135 control animals. Somatotropes from restricted fetuses were significantly (p<0.001) larger at Day 78. Nutrient restriction increased the density (p<0.001) and percentage (p<0.05) of substance P-immunoreactive cells Day 135 fetuses. Similarly, the proportion of somatotropes that expressed substance P was significantly (p<0.05) increased by nutrient restriction in the Day 135 fetuses. Although nearly two thirds of substance P-immunoreactive cells co-expressed GH, there was no significant effect of treatment on this co-expression. Additional studies are required to determine if other components of the neuroendocrine GH axis are affected by this nutritional insult, if the alterations that we have observed, particularly in the tachykinin system, persist into adulthood and, importantly, what are the long-term consequences of an altered GH axis.

Animals↗

PubMed2005

Effects of a 14-day period of hindpaw sensory restriction on mRNA and protein levels of NGF and BDNF in the hindpaw primary somatosensory cortex.

Neurotrophins have been reported to play an important role in neuronal plasticity and to be regulated by neuronal activity and/or neurotransmitters. Recently, we have shown that hindpaw sensory restriction induces a cortical reorganisation in the hindpaw primary somatosensory cortex, and that acetylcholine plays a significant role in this process. Sensory restriction was obtained by hindlimb suspension for 14 days. In this study, we examined the effects of a long period of hindpaw sensory restriction on the NGF and BDNF mRNA and protein expressions in the hindpaw somatosensory cortex. mRNA and protein levels were assessed by RT-PCR and ELISA, respectively. First, we found that NGF and BDNF mRNA relative levels increased after hindpaw sensory restriction. Second, the level of NGF protein increased, whereas that of BDNF remained unchanged. This differential response of NGF and BDNF proteins to sensory restriction suggested different levels of gene regulation, i.e., at pretranslational or posttranslational states. Moreover, inasmuch as our results differ from other models of sensory restriction (dark rearing, whisker removal, etc.), we hypothesized that the regulation of neurotrophin expression is dependent on the type and duration of the sensory restriction. In conclusion, we argue that neuronal plasticity induced by hindpaw sensory restriction requires neurotrophin expression.

Animals↗