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Biomedical subjects

G Meneses

Publications and source records attributed to G Meneses.

16 recordsLinked to original sources

Further evaluation of the synthetic peptide vaccine S3Pvac against Taenia solium cysticercosis in pigs in an endemic town of Mexico.

Taenia solium cysticercosis is a parasitic disease frequently affecting human health and the pig industry in many developing countries. A synthetic peptide vaccine (designated S3Pvac) against porcine cysticercosis has been developed previously as an aid to interrupt transmission and has been shown to be effective. The results of the present study support the effectiveness of the vaccine under endemic field conditions. However, given the time-frame of the vaccination trial, no changes in the local levels of transmission were detectable before and after vaccination using sentinel pigs. Thus, this investigation shows the limited usefulness of single vaccination as the sole means of interrupting Taenia solium transmission in an endemic region.

Animals↗

Intrahepatic DNA vaccination: unexpected increased resistance against murine cysticercosis induced by non-specific enhanced immunity.

Experimental murine cysticercosis caused by Taenia crassiceps has proved to be a useful model with which to test the efficacy of new vaccine candidates and delivery systems against pig cysticercosis. A high level of protection against murine cysticercosis was previously observed by intramuscular or intradermal DNA immunization with the use of the sequence of the recombinant KETc7 antigen cloned in pcDNA3 (pTc-sp7). To determine the effect of KETc7 differential expression in DNA vaccination, KETc7 was cloned in pGEM 11Zf(+) under the control of the tissue-specific regulatory promoter phosphoenolpyruvate carboxykinase (pPc-sp7). A high level of protection was induced by intrahepatic immunization with pPc-sp7, pTc-sp7 and the empty vector in the absence of any specific immunity. The empty vector pGEM 11Zf(+), the plasmid with the highest content of CpG sequences, provided to the most efficient protection. This protection was related to an increased number of splenocytes, enhanced nonspecific splenocyte proliferation, and intensified intrahepatic INF-gamma production. Overall, intrahepatic plasmid CpG-DNA immunization provokes an exacerbated nonspecific immune response that can effectively control Taenia crassiceps cysticercosis.

Animals↗

Effective protection against experimental Taenia solium tapeworm infection in hamsters by primo-infection and by vaccination with recombinant or synthetic heterologous antigens.

The disease caused by Taenia solium is progressively being recognized as a growing global threat for public human health and pig husbandry that requires the development of effective control measures. A central participant in the taeniasis/cysticercosis transmission network is the human carrier of the adult tapeworm because of its great potential in spreading the infection. Herein, evidence is presented that a primary infection of golden hamsters with orally administered T. solium cysticerci improved the host's resistance against a secondary infection. Likewise, previous vaccination increased the hamster's resistance. Similar high levels of protection (> 78%) were induced by systemic or oral vaccination with the S3Pvac anticysticercosis synthetic peptide vaccine or the highly immunogenic recombinant chimera based on the protective peptide KETc1 bound to Brucella spp. lumazine synthase (BLS-KETc1). Increased resistance after primo-infection and vaccination possibly results from changes in the immune conditions prevailing in the host's intestine. The contribution to protection from the KETc1 and BLS epitopes in a chimeric vaccine is under study. Preventive vaccination of definitive hosts of T. solium against the tapeworm, the most relevant step in the taeniasis/cysticercosis transmission, may greatly impact the dynamics of endemic disease and has not been studied or tried previously.

Animals↗

Effect of oral zinc supplementation upon Taenia crassiceps murine cysticercosis.

The effect of zinc supplementation on Taenia crassiceps murine cysticercosis was studied in susceptible BALB/cAnN mice. Female offspring of mice supplemented with high zinc throughout gestation and lactation were intraperitoneally infected with T. crassiceps cysticerci. Offspring from nonsupplemented mothers were used as controls. Significantly fewer parasites were recovered from zinc-supplemented mice (Zsm) 30 days after infection. Increased resistance was not related to the IgG antibody response. At early stages of infection, T cells from Zsm proliferated to T. crassiceps antigens, whereas cells from control mice did not respond. Infection caused in both groups a decrease in CD3+ cell percentages, which was more pronounced in the controls, and paralleled by a decrease in CD8+ cells; CD3+ and CD8+ percentages returned to normal levels at later stages of infection. In contrast, the CD4+ subpopulation only decreased in control mice. Intracellular cytokine determinations indicate that zinc supplementation favored a stronger and persistent type-1 T cell response in cysticerci-infected mice, which probably participates in the observed increased resistance.

Administration, Oral↗

Renal protection in patients undergoing cardiopulmonary bypass with preoperative abnormal renal function.

UNLABELLED: We prospectively studied the effects of renal protection intervention in 17 patients with preoperative abnormal renal function (plasma creatinine > 1.5 mg/dL) scheduled for elective coronary surgery. Patients were randomized to either dopamine 2.0 micrograms.kg-1.min-1 (Group 1, n = 10) or perfusion pressure > 70 mm Hg during cardiopulmonary bypass (CPB) (Group 2, n = 7). Glomerular filtration rate and effective renal plasma flow were measured with inulin and 125I-hippuran clearances before the induction of anesthesia, after sternotomy and before CPB, during hypo- and normothermic CPB, after sternal closure, and 1 h postoperatively. Plasma and urine electrolytes were measured, and free water, osmolar, and creatinine clearances, as well as fractional excretion of sodium and potassium, were calculated before and after surgery. Significant differences between groups were found before CPB for glomerular filtration rate (higher in Group 1), urine output (2.0 vs 0.29 mL/min in Group 1 versus Group 2), urinary creatinine (66 vs 175 mg/dL), urinary osmolarity (370 vs 627 mOsm/L), osmolar clearance (2.1 vs 0.7 mL/min), and urinary potassium (33 vs 71 mEq/L). There were no differences between groups during hypo- and normothermic CPB. After CPB, the only difference was a slightly higher urinary creatinine in Group 2. Renal plasma flow was lower than normal in all patients before the induction of anesthesia. A nonsignificant trend toward increased flow was seen during hypothermic CPB. Filtration fraction was high before CPB, which suggests efferent arteriolar vasoconstriction, descending toward normal during and after CPB. The same pattern of changes was present in both groups. In conclusion, there were no clinically relevant differences between the two treatment modalities during and after CPB. However, significant differences were observed before CPB, when dopamine seemed to partially revert renal vasoconstriction. IMPLICATIONS: Two protective interventions were compared in patients undergoing heart surgery to prevent deterioration of renal function; these were dopamine infusion throughout the operation and phenylephrine infusion during cardiopulmonary bypass. We found clinically relevant differences only during surgery before cardiopulmonary bypass.

Aged↗

Thymostimulin increases natural cytotoxic activity in patients with breast cancer.

The effect of thymostimulin on the Natural Killer (NK) cytotoxic activity of peripheral blood mononuclear cells (PBMC) was investigated in 15 patients with breast cancer after finishing or during chemotherapy (CAF) and in 10 healthy controls. PBMC from these subjects were incubated in the presence of thymostimulin for varying periods of time (18 h or 5 days), and then used as effector cells against 51Cr-radiolabeled NK-sensitive (K-562) and NK-resistant (JY) target cells in cytotoxicity assays. No significant differences were observed between the NK-activity from breast cancer patients and healthy controls. Thymostimulin induced a dose- and time-dependent cytotoxic enhancing effect on the cytotoxic activity of PBMC from these patients against NK-sensitive K562 target cells. The thymostimulin (1000 ng/ml) significantly enhanced cytotoxic activity in PBMC from breast cancer patients who had previously received chemotherapy (p = 0.0277) against NK-sensitive cells. This increase was not statistically significant neither in PBMC from patients receiving chemotherapy nor in healthy controls (p > 0.05 in both cases). The incubation of PBMC from patients with breast cancer was not associated to a significant enhancement of the cytotoxic activity against NK-resistant target cells (p > 0.05). We also found that thymostimulin could synergize with interleukin-2 in inducing NK cytotoxic activity in PBMC after 18 h of culture (p = 0.0277). In conclusion, we have demonstrated that thymostimulin enhances the natural killer cytotoxic activity of PBMC from patients with breast cancer who have previously received chemotherapy.

Adjuvants, Immunologic↗

Arterial pressure-flow relationship in patients undergoing cardiopulmonary bypass.

We determined the arterial pressure-flow relationship experimentally by means of step changes of blood flow in 30 adult patients undergoing cardiopulmonary bypass (CPB). Anesthesia technique was uniform. CPB was nonpulsatile; hypothermia to 25-28 degrees C, and hemodilution to 18%-25% hematocrit were used. During stable bypass, mean arterial pressure was recorded first with blood flow 2.2 L.min-1.m-2. Flow was then increased to 2.9 L.min-1.m-2 for 10 s and reverted to baseline for 1 min. Then it was decreased to 1.45 L.min-1.m-2 for 10 s, and reverted to baseline for 1 min. Subsequently, it was decreased to 0.73 L.min-1.m-2 for 10 s and then reverted to baseline. Similar sets of measurements were repeated after 0.25 mg of phenylephrine and once the patient was rewarmed. The pressure-flow function was individually determined by regression, and the critical pressure estimated by extrapolation to zero flow. All patients had zero-flow critical pressure during hypothermia, with a mean value of 21.8 +/- 6.4 mm Hg (range 8.8-38.9). It increased after 0.25 mg phenylephrine to 25.4 +/- 7.2 mm Hg (range 12.2-43.9, P < 0.001). During normothermia, critical pressure was 21.2 +/- 5 mm Hg (range 13.4-30.9), not significantly different from hypothermia. During hypothermia, the slope of the pressure-flow function (i.e., resistance) was 14.9 +/- 3.5 mm Hg.L-1.min-1.m-2 (range 7.6-22.1). It increased significantly (P < 0.001) after phenylephrine, to 19.7 +/- 6.2 mm Hg.L-1.min-1.m-2 (range 11.4-40.5), and returned to 15.4 +/- 3.4 mm Hg.L-1.min-1.m-2 (range 10.1-24.2) during normothermic bypass. Systemic vascular resistance appeared to vary reciprocally with blood flow, although this finding may represent a mathematical artifact, which can be avoided by using zero-flow critical pressure in the vascular resistance equation.

Adult↗

Comparison of isoflurane, halothane and fentanyl in patients with decreased ejection fraction undergoing coronary surgery.

The aim of the study was to compare three anaesthetic agents in patients with ejection fraction below 0.40 subjected to coronary revascularization surgery. Twenty five elective coronary surgical patients with ejection fraction below 0.40 were prospectively studied. Premedication was pethidine 1 mg/kg and induction was fentanyl 0.03 mg/kg and pancuronium 0.1 mg/kg. The patients were randomized to one of three maintenance techniques (fentanyl, isoflurane or halothane). Radial arterial pressure, heart rate, right atrial pressure, pulmonary arterial and occluded pressures, and thermodilution cardiac output were measured, and cardiac index and resistance calculated, at the following times: before induction; 5 min after intubation; 2 min after sternotomy; immediately after discontinuation of bypass; 15 min afterwards; immediately after sternal closure; during suture of the skin; 5 min after arrival in the postoperative care unit; and 60 min postoperatively. Mean arterial pressure decreased significantly in the isoflurane group and nonsignificantly in the halothane group after induction. Cardiac index decreased significantly in the isoflurane group and nonsignificantly in the halothane group after induction and after sternotomy. Neither pressure nor flow decreased in patients receiving fentanyl. Following weaning from cardiopulmonary bypass, systemic vascular resistance decreased significantly in all groups. Cardiac index, however, did not increase above control values and arterial pressure consequently decreased; there was no significant difference between groups.

Adjuvants, Anesthesia↗

Effects of extracorporeal circulation on renal function in coronary surgical patients.

We prospectively studied perioperative changes of renal function in 12 previously normal patients (plasma creatinine < 1.5 mg/dL) scheduled for elective coronary surgery. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured with inulin and 125I-hippuran clearances before induction of anesthesia, before cardiopulmonary bypass (CPB), during hypo- and normothermic CPB, after sternal closure, and 1 h postoperatively. Renal and systemic vascular resistances were calculated. Urinary N-acetyl-beta-D-glucosaminidase (NAG) and plasma and urine electrolytes were measured, and free water, osmolal, and creatinine clearances, and fractional excretion of sodium and potassium were calculated before and after surgery. 125I-hippuran clearance was lower than normal in all patients before surgery. During hypothermic CPB, ERPF increased significantly (from 261 +/- 107 to 413 +/- 261 mL/min) and returned toward baseline values during normothermia. GFR was normal before and after surgery and decreased nonsignificantly during CPB. Filtration fraction was above normal before surgery and decreased significantly during CPB (0.38 +/- 0.09 to 0.18 +/- 0.06). Renal vascular resistance (RVR) was high before surgery and further increased after sternotomy (from 18,086 +/- 6849 to 30,070 +/- 24,427 dynes.s.cm-5), decreasing during CPB to 13,9647 +/- 14,662 dynes.s.cm-5. Urine NAG, creatinine, and free water clearances were normal in all patients both pre- and postoperatively. Osmolal clearance and fractional excretion of sodium increased postoperatively from 1.54 +/- 0.06 to 12.47 4/- 11.37 mL/min, and from 0.44 +/- 0.3 to 6.07 +/- 6.27, respectively. We conclude that renal function does not seem to be adversely affected by CPB.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Molecular characterization of human Ig heavy chain DIR genes.

Antibody VDJ recombination is ensured by evolutionarily conserved recombination signals (RS). The 12/23 rule postulates that only gene segments with asymmetrically spaced RS recombine with one another. Two unusually long D genes (170 bp) with irregular RS (DIR) have been reported in humans and have been postulated to participate actively in VDJ recombination, thus frequently contributing to the Ab heavy chain third hypervariable region (CDR3). However, the limited sequence information retained in the CDR3 along with significant sequence diversity has precluded an accurate assessment of the actual role and genomic diversity of DIR genes. Furthermore, DIR genes pose an interesting puzzle in terms of their precise mechanism of recombination because they possess multiple and imperfect RS, often located up to 30 bp away from the recombining fragment within the DIR coding region. Here we present conclusive evidence for the existence of additional human germ-line DIR genes and preliminary evidence that suggests the absence of DIR-like sequences in nonprimate animals. We also show that DIR genes are under the transcriptional control of VH-independent promoters and have the potential to encode a D mu protein of 105 amino acids. Finally, DIR genes seem at least in early fetal life to recombine preferentially through the conventional 3' RS.

Animals↗

Thermoregulatory vasoconstriction increases the difference between femoral and radial arterial pressures.

OBJECTIVE: Thermoregulatory vasoconstriction locally increases arterial wall tension and arteriolar resistance, thereby altering physical properties of the arteries. The arterial pressure waveform is an oscillatory phenomenon related to those physical characteristics; accordingly, we studied the effects of thermoregulatory vasomotion on central and distal arterial pressures, using three hydraulic coupling systems having different dynamic responses. METHODS: We studied 7 healthy volunteers. Central arterial pressure was measured from the femoral artery and distal pressure was measured from the radial artery, using 10.8-cm long, 20-gauge catheters. Three hydraulic coupling systems were used: (1) a 10-cm-long, 2-mm internal diameter connector; (2) a 150-cm-long, 1-mm internal diameter connector (Combidyn 520-5689, B. Braun, Melsungen, Germany); (3) a 180-cm long, 2-mm internal diameter connector (Medex MX564 and MX562, Medex Inc., Hillard, OH). Brachial artery pressure was measured oscillometrically. Core temperature was measured at the tympanic membrane. The vasomotor index, defined as finger temperature minus room temperature, divided by core temperature minus room temperature, was used to estimate the degree of vasoconstriction. Constriction was considered near maximal when the index was less than 0.1, and minimal when it exceeded 0.75. Measurements were taken every 3 min. Baseline readings were obtained when subjects were warm. They then were cooled by exposure to 20 degrees C to 22 degrees C room air and a circulating-water mattress set at 4 degrees C until index was less than 0.1. They then were rewarmed by increasing water temperature to 42 degrees C and adding a forced-air warmer until the vasomotor index exceeded 0.75. Data were analyzed by ANOVA and linear regression. RESULTS: Thermoregulatory vasoconstriction was associated with marked arterial pressure waveform changes. Radial pressure showed, in lieu of a dicrotic notch, large oscillations of decreasing amplitude. Femoral pressure showed a single diastolic oscillation of smaller amplitude. The waveforms appeared different, depending on the hydraulic coupling system used, artifact being more marked with the longer connectors. On the average, radial systolic pressure exceeded femoral systolic pressure during vasoconstriction; however, during vasodilatation, femoral systolic pressure exceeded radial systolic pressure (p < 0.05). Oscillometric measurements underestimated systolic pressure, and did so more markedly during vasoconstriction. There were no differences in the values of mean and diastolic pressures. CONCLUSION: Thermoregulatory vasoconstriction alters radial arterial pressure waveform, artifactually increasing its peak systolic pressure compared with the femoral artery. Poor dynamic responses of recording systems further distort the waveforms. Consequently, radial artery pressure may be misleading in vasoconstricted patients.

Adult↗

Renal function and cardiopulmonary bypass: effect of perfusion pressure.

Controversy continues as to whether hypotension during cardiopulmonary bypass (CPB) impairs intraoperative and postoperative renal function. Therefore, 21 patients with normal renal function (plasma creatinine less than 1.2 mg/dL, creatinine clearance greater than 70 mL/min), aged 50 to 70 years, without associated pathology, scheduled for elective coronary surgery were studied prospectively. Patients were randomized into two groups: group 1 included 14 patients whose arterial blood pressure during CPB was left untreated, and group 2 consisted of 7 patients who received phenylephrine to maintain their arterial pressure above 70 mmHg. Plasma and urine creatinine, sodium, potassium, and osmolality were measured preoperatively, intraoperatively and postoperatively. Creatinine, osmolal and free water clearances, and excreted sodium fraction were calculated. Plasma creatinine remained normal throughout the study in all patients. Creatinine clearances were similar preoperatively (101.9 +/- 36.7 in group 1 and 120.6 +/- 50.7 mL/min in group 2). In group 1, creatinine clearance decreased during CPB to 88.7 +/- 39.7 mL/min, whereas in group 2 it increased to 157.6 +/- 79.5 mL/min; the difference between groups was significant. Early postoperatively, there was no difference: 136.2 +/- 86.6 mL/min in group 1 and 100 +/- 21.4 mL/min in group 2. One week postoperatively, values were 100.5 +/- 37.9 and 101.9 +/- 18.4, respectively. There was a significant correlation between the creatinine clearance and perfusion pressure intraoperatively, but not postoperatively. Osmolal clearance also correlated with perfusion pressure intraoperatively, but it was significantly lower in the phenylephrine group postoperatively. Postoperative renal function was normal in all patients; no deleterious effect of a low arterial pressure during bypass could be identified.

Aged↗