Serum Vitamins in Adult Patients With Short Bowel Syndrome Receiving Intermittent Parenteral Nutrition

Background: Short bowel syndrome (SBS) occurs after massive intestinal resection, and parenteral nutrition (PN) therapy may be necessary even after a period of adaptation. The purpose of this study was to determine the vitamin status in adults with SBS receiving intermittent PN. Methods: The study was conducted on hospitalized adults with SBS who were receiving intermittent PN therapy (n = 8). Nine healthy volunteers, paired by age and sex, served as controls. Food ingestion, anthropometry, plasma folic acid, and vitamins B(12), C, A, D, E, and K were evaluated. Results: The levels of vitamins A, D, and B(12) in both groups were similar. SBS patients presented higher values of folic acid (21.3 +/- 4.4 vs 14.4 +/- 5.2, P = .01) and lower values of vitamin C (0.9 +/- 0.4 vs 1.2 +/- 0.3 mg/dL, P = .03), alpha-tocopherol (16.3 +/- 3.4 vs 24.1 +/-+/- 2.7 mu mol/L, P < .001), and phylloquinone (0.6 +/- 0.2 vs 1.0 +/- 0.5 nmol/L, P < .03). Eight-seven percent of patients had vitamin D deficiency, and all patients presented with serum vitamin E levels below reference values. Conclusions: Despite all efforts to offer all the nutrients mentioned above, SBS patients had lower serum levels of vitamins C, E, and K, similar to those observed in patients on home PN. These findings suggest that the administered vitamins were not sufficient for the intermittent PN scheme and that individual adjustments are needed depending on the patient`s vitamin status. (JPEN J Parenter Enteral Nutr. 2011;35:493-498)

Sympathetic-mediated hypertension of awake juvenile rats submitted to chronic intermittent hypoxia is not linked to baroreflex dysfunction

In the present study, we evaluated the mechanisms underpinning the hypertension observed in freely moving juvenile rats submitted to chronic intermittent hypoxia (CIH). Male juvenile Wistar rats (20-21 days old) were submitted to CIH (6% O(2) for 40 s every 9 min, 8 h day(-1)) for 10 days while control rats were maintained in normoxia. Prior to CIH, baseline systolic arterial pressure (SAP), measured indirectly, was similar between groups (86 +/- 1 versus 87 +/- 1 mmHg). After exposure to CIH, SAP recorded directly was higher in the CIH (n = 28) than in the control group (n = 29; 131 +/- 3 versus 115 +/- 2 mmHg, P < 0.05). This higher SAP of CIH rats presented an augmented power of oscillatory components at low (10.05 +/- 0.91 versus 5.02 +/- 0.63 mmHg(2), P < 0.05) and high (respiratory-related) frequencies (12.42 +/- 2.46 versus 3.28 +/- 0.61 mmHg(2), P < 0.05) in comparison with control animals. In addition, rats exposed to CIH also exhibited an increased cardiac baroreflex gain (-3.11 +/- 0.08 versus -2.1 +/- 0.10 beats min(-1) mmHg(-1), P < 0.0001), associated with a shift to the right of the operating point, in comparison with control rats. Administration of hexamethonium (ganglionic blocker, i.v.), injected after losartan (angiotensin II type 1 receptor antagonist) and [beta-mercapto-beta,beta-cyclopenta-methylenepropionyl(1), O-Me-Tyr(2), Arg(8)]-vasopressin (vasopressin type 1a receptor antagonist), produced a larger depressor response in the CIH (n = 8) than in the control group (n = 9; -49 +/- 2 versus -39 +/- 2 mmHg, P < 0.05). Fifteen days after the cessation of exposure to CIH, the mean arterial pressure of CIH rats returned to normal levels. The data indicate that the sympathetic-mediated hypertension observed in conscious juvenile rats exposed to CIH is not secondary to a reduction in cardiac baroreflex gain and exhibits a higher respiratory modulation, indicating that an enhanced respiratory-sympathetic coupling seems to be the major factor contributing to hypertension in rats exposed to CIH.

Intermittent hypoxia-induced sensitization of central chemoreceptors contributes to sympathetic nerve activity during late expiration in rats

Molkov YI, Zoccal DB, Moraes DJ, Paton JF, Machado BH, Rybak IA. Intermittent hypoxia-induced sensitization of central chemoreceptors contributes to sympathetic nerve activity during late expiration in rats. J Neurophysiol 105: 3080-3091, 2011. First published April 6, 2011; doi:10.1152/jn.00070.2011.-Hypertension elicited by chronic intermittent hypoxia (CIH) is associated with elevated activity of the thoracic sympathetic nerve (tSN) that exhibits an enhanced respiratory modulation reflecting a strengthened interaction between respiratory and sympathetic networks within the brain stem. Expiration is a passive process except for special metabolic conditions such as hypercapnia, when it becomes active through phasic excitation of abdominal motor nerves (AbN) in late expiration. An increase in CO(2) evokes late-expiratory (late-E) discharges phase-locked to phrenic bursts with the frequency increasing quantally as hypercapnia increases. In rats exposed to CIH, the late-E discharges synchronized in AbN and tSN emerge in normocapnia. To elucidate the possible neural mechanisms underlying these phenomena, we extended our computational model of the brain stem respiratory network by incorporating a population of presympathetic neurons in the rostral ventrolateral medulla that received inputs from the pons, medullary respiratory compartments, and retrotrapezoid nucleus/parafacial respiratory group (RTN/pFRG). Our simulations proposed that CIH conditioning increases the CO(2) sensitivity of RTN/pFRG neurons, causing a reduction in both the CO(2) threshold for emerging the late-E activity in AbN and tSN and the hypocapnic threshold for apnea. Using the in situ rat preparation, we have confirmed that CIH-conditioned rats under normal conditions exhibit synchronized late-E discharges in AbN and tSN similar to those observed in control rats during hypercapnia. Moreover, the hypocapnic threshold for apnea was significantly lowered in CIH-conditioned rats relative to that in control rats. We conclude that CIH may sensitize central chemoreception and that this significantly contributes to the neural impetus for generation of sympathetic activity and hypertension.

INTERMITTENT ACTIVATION OF PERIPHERAL CHEMORECEPTORS IN AWAKE RATS INDUCES Fos EXPRESSION IN ROSTRAL VENTROLATERAL MEDULLA-PROJECTING NEURONS IN THE PARAVENTRICULAR NUCLEUS OF THE HYPOTHALAMUS

Despite the well-established sympathoexcitation evoked by chemoreflex activation, the specific sub-regions of the CNS underlying such sympathetic responses remain to be fully characterized. In the present study we examined the effects of intermittent chemoreflex activation in awake rats on Fos-immunoreactivity (Fos-ir) in various subnuclei of the paraventricular nucleus of the hypothalamus (PVN), as well as in identified neurosecretory preautonomic PVN neurons. In response to intermittent chemoreflex activation, a significant increase in the number of Fos-ir cells was found in autonomic-related PVN subnuclei, including the posterior parvocellular, ventromedial parvocellular and dorsal-cap, but not in the neurosecretory magnocellular-containing lateral magnocellular subnucleus. No changes in Fos-ir following chemoreflex activation were observed in the anterior PVN subnucleus. Experiments combining Fos immunohistochemistry and neuronal tract tracing techniques showed a significant increase in Fos-ir in rostral ventrolateral medulla (RVLM)-projecting (PVN-RVLM), but not in nucleus of solitarii tract (NTS)-projecting PVN neurons. In summary, our results support the involvement of the PVN in the central neuronal circuitry activated in response to chemoreflex activation, and indicate that PVN-RVLM neurons constitute a neuronal substrate contributing to the sympathoexcitatory component of the chemoreflex. Published by Elsevier Ltd on behalf of IBRO.

Increased sympathetic outflow in juvenile rats submitted to chronic intermittent hypoxia correlates with enhanced expiratory activity

Chronic intermittent hypoxia (CIH) in rats produces changes in the central regulation of cardiovascular and respiratory systems by unknown mechanisms. We hypothesized that CIH (6% O(2) for 40 s, every 9 min, 8 h day(-1)) for 10 days alters the central respiratory modulation of sympathetic activity. After CIH, awake rats (n = 14) exhibited higher levels of mean arterial pressure than controls (101 +/- 3 versus 89 +/- 3 mmHg, n = 15, P < 0.01). Recordings of phrenic, thoracic sympathetic, cervical vagus and abdominal nerves were performed in the in situ working heart-brainstem preparations of control and CIH juvenile rats. The data obtained in CIH rats revealed that: (i) abdominal (Abd) nerves exhibited an additional burst discharge in late expiration; (ii) thoracic sympathetic nerve activity (tSNA) was greater during late expiration than in controls (52 +/- 5 versus 40 +/- 3%; n = 11, P < 0.05; values expressed according to the maximal activity observed during inspiration and the noise level recorded at the end of each experiment), which was not dependent on peripheral chemoreceptors; (iii) the additional late expiratory activity in the Abd nerve correlated with the increased tSNA; (iv) the enhanced late expiratory activity in the Abd nerve unique to CIH rats was accompanied by reduced post-inspiratory activity in cervical vagus nerve compared to controls. The data indicate that CIH rats present an altered pattern of central sympathetic-respiratory coupling, with increased tSNA that correlates with enhanced late expiratory discharge in the Abd nerve. Thus, CIH alters the coupling between the central respiratory generator and sympathetic networks that may contribute to the induced hypertension in this experimental model.

Effect of low-dose combined oral contraceptive on aerobic capacity and anaerobic threshold level in active and sedentary young women

Background: The purpose of this study was to evaluate the effect of long-term use of oral contraceptives (DC) containing 0.20 mg of ethinylestradiol (EE) combined with 0.15 mg of gestodene (GEST) on the peak aerobic capacity and at the anaerobic threshold (AT) level in active and sedentary young women. Study Design: Eighty-eight women (23 +/- 2.1 years old) were divided into four groups active-OC (G1), active-NOC (G2), sedentary-OC (G3) and sedentary-NOC (G4) and were submitted to a continuous ergospirometric incremental test on a cycloergometer with 20 to 25 W min(-1) increments. Data were analyzed by two-way ANOVA with Tukey post hoc test. Level of significance was set at 5%. Results: The OC use effect for the variables relative and absolute oxygen uptake VO(2) mL kg(-1) min(-1); VO(2), L min(-1), respectively), carbon dioxide output (VCO(2), L min(-1)), ventilation (VE, L min(-1)), heart rate (HR, bpm), respiratory exchange ratio (RER) and power output (W) data, as well as the interaction between OC use and exercise effect on the peak of test and at the AT level did not differ significantly between the active groups (G1 and G2) and the sedentary groups (G3 and G4). As to the exercise effect, for all variables studied, it was noted that the active groups presented higher values for the variables VO(2), VCO(2), VE and power output (p<.05) than the sedentary groups. The RER and HR were similar (p>.05) at the peak and at the AT level between G1 vs. G3 and G2 vs. G4. Conclusions: Long-term use of OC containing EE 0.20 mg plus GEST 0.15 mg does not affect aerobic capacity at the peak and at the AT level of exercise tests. (C) 2010 Elsevier Inc. All rights reserved.

Benefits of the Intermittent Use of 6-Mercaptopurine and Methotrexate in Maintenance Treatment for Low-Risk Acute Lymphoblastic Leukemia in Children: Randomized Trial From the Brazilian Childhood Cooperative Group Protocol ALL-99

Purpose To describe event-free survival (EFS) and toxicities in children with low-risk acute lymphoblastic leukemia (ALL) assigned to receive either continuous 6-mercaptopurine (6-MP) and weekly methotrexate (MIX) or intermittent 6-MP with intermediate-dose MTX, as maintenance treatment. Patients and Methods Between October 1, 2000, and December 31, 2007, 635 patients with low-risk ALL were enrolled onto Brazilian Childhood Cooperative Group for ALL Treatment (GBTLI) ALL-99 protocol. Eligible children (n=544) were randomly allocated to receive either continuous 6-ME/MIX (group 1, n 272) or intermittent 6-MP (100 mg/m(2)/d for 10 days, with 11 days resting) and MIX (200 mg/m(2) every 3 weeks; group 2, n = 272). Results The 5-year overall survival (OS) and EFS were 92.5% +/- 1.5% SE and 83.6% +/- 2.1% SE, respectively. According to maintenance regimen, the OS was 91.4% +/- 2.2% SE (group 1) and 93.6% +/- 2.1% SE (group 2; P=.28) and EFS 80.9% +/- 3.2% SE (group 1) and 86.5% +/- 2.8% SE (group 2; P=.089). Remarkably, the intermittent regimen led to significantly higher EFS among boys (85.7% v 74.9% SE; P=027), while no difference was seen for girls (87.0% v 88.8% SE; P=.78). Toxic episodes were recorded in 226 and 237 children, respectively. Grade 3 to 4 toxic events for groups 1 and 2 were, respectively, 273 and 166 for hepatic dysfunction (P=.002), and 772 and 636 for hematologic episodes (P=.005). Deaths on maintenance were: seven (group 1) and one (group 2). Conclusion The intermittent use of 6-MP and MIX in maintenance is a less toxic regimen, with a trend toward better long-term EFS. Boys treated with the intermittent schedule had significantly better EFS.

Thermostable variants of the recombinant xylanase A from Bacillus subtilis produced by directed evolution show reduced heat capacity changes

Directed evolution techniques have been used to improve the thermal stability of the xylanase A from Bacillus subtilis (XylA). Two generations of random mutant libraries generated by error prone PCR coupled with a single generation of DNA shuffling produced a series of mutant proteins with increasing thermostability. The most Thermostable XylA variant from the third generation contained four mutations Q7H, G13R, S22P, and S179C that showed an increase in melting temperature of 20 degrees C. The thermodynamic properties Of a representative subset of nine XylA variants showing a range of thermostabilities were measured by thermal denaturation as monitored by the change in the far ultraviolet circular dichroism signal. Analysis of the data from these thermostable variants demonstrated a correlation between the decrease in the heat capacity change (Delta C(p)) with an increase in the midpoint of the transition temperature (T(m)) on transition from the native to the unfolded state. This result could not be interpreted within the context of the changes in accessible surface area of the protein on transition from the native to unfolded states. Since all the mutations are located at the surface of the protein, these results suggest that an explanation of the decrease in Delta C(p) on should include effects arising from the prot inlsolvent interface.

Relationship among eccentric hip and knee torques, symptom severity and functional capacity in females with patellofemoral pain syndrome

Objective: To determine the relationships between eccentric hip and knee torques, symptom severity and functional capacity in females with patellofemoral pain syndrome (PFPS). Design: Within-subject correlational study. Setting: University biomechanics laboratory. Participants: 10 females diagnosed with PFPS. Main outcome measures: Eccentric strength of the hip abductors and lateral rotators, and knee extensors were assessed using an isokinetic dynamometer. A 10-cm visual analog scale was used to determine usual knee pain in the last week. The Anterior Knee Pain Scale (AKPS) was used to determine the functional capacity of the patients. Results: The study found that the greater the eccentric knee extensor and hip lateral rotator torques, the higher the functional capacity of the patients (p = 0.02, r = 0.72; p = 0.02, r = 0.72). It was also shown that the greater hip lateral rotator torque, the less the usual pain reported in the last week (p = 0.004, r = -0.84). Despite the lack of statistical significance (p = 0.11), it was also found a modest negative relationship between the eccentric knee extensor torque and the usual pain reported in the last week (r = -0.56) that was considered clinically meaningful (d = 1.4). Conclusions: This study showed that eccentric knee extensor and hip lateral rotator torques were associated with functional capacity and pain level in females with PFPS. Further investigations should be carried out to verify the effects of an intervention program focused on the eccentric action of these muscles with respect to the symptoms in patients with PFPS. (C) 2011 Elsevier Ltd. All rights reserved.

Fracture resistance of endodontically treated teeth with different heights of crown ferrule restored with prefabricated carbon fiber post and composite resin core by intermittent loading

This study evaluated the fracture resistance of endodontically treated teeth restored with prefabricated carbon fiber posts and varying quantities of coronal dentin. Sixty freshly extracted upper canines were randomly divided into groups of 10 teeth each. The specimens were exposed to 250,000 cycles in a controlled chewing simulator. All intact specimens were subjected to a static load (N) in a universal testing machine at 45 degrees to the long axis. Data were analyzed by 1-way analysis of variance and Tukey test (alpha = .05). Significant differences (P < .001) were found among the mean fracture forces of the test groups (positive control, 0 mm, 1 mm, 2 mm, 3 mm, and negative control groups: 1022.82 N, 1008.22 N, 1292.52 N, 1289.19 N, 1255.38 N, and 1582.11, respectively). These results suggested that the amount of coronal dentin did not significantly increase the fracture resistance of endodontically treated teeth restored with prefabricated carbon fiber post and composite resin core. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2008;106:e52-e57)