Search PubMed⌕ Search

Biomedical subjects

N Garcia

Publications and source records attributed to N Garcia.

At least 37 records · Page 2Linked to original sources

Laboratory assessment of hepatic hemodynamics.

Although the study of hepatic circulation is complicated by the dual blood supply and complex anatomy of the liver, many distinct methods are available to facilitate its study. Before embarking on an investigation of hepatic hemodynamics, the investigator must be familiar with the available methods and their applications. All methods have their own attributes and limitations. No one method is superior to the others, but, depending on the aspect of hepatic hemodynamics to be investigated, a particular methodology may yield distinct advantages.

Animals↗

Endocannabinoids acting at vascular CB1 receptors mediate the vasodilated state in advanced liver cirrhosis.

Advanced cirrhosis is associated with generalized vasodilation of unknown origin, which contributes to mortality. Cirrhotic patients are endotoxemic, and activation of vascular cannabinoid CB1 receptors has been implicated in endotoxin-induced hypotension. Here we show that rats with biliary cirrhosis have low blood pressure, which is elevated by the CB1 receptor antagonist SR141716A. The low blood pressure of rats with CCl4-induced cirrhosis was similarly reversed by SR141716A, which also reduced the elevated mesenteric blood flow and portal pressure. Monocytes from cirrhotic but not control patients or rats elicited SR141716A-sensitive hypotension in normal recipient rats and showed significantly elevated levels of anandamide. Compared with non-cirrhotic controls, in cirrhotic human livers there was a three-fold increase in CB1 receptors on isolated vascular endothelial cells. These results implicate anandamide and vascular CB1 receptors in the vasodilated state in advanced cirrhosis and indicate a novel approach for its management.

Animals↗

Modified seven-day, quadruple therapy as a first line Helicobacter pylori treatment.

BACKGROUND: Cure rates of 7-day triple therapy seem to be decreasing. Quadruple therapies may be an alternative, although their complex administration makes patient acceptance difficult. OBJECTIVE: To test the usefulness of a thrice a day, quadruple therapy to cure Helicobacter pylori infection. PATIENTS AND METHODS: A total of 122 consecutive patients with peptic ulcer and Helicobacter pylori infection were treated with omeprazole 20 mg b.d., tetracycline chlorhydrate 500 mg t.d.s., metronidazole 500 mg t.d.s., and bismuth subcitrate 120 mg t.d.s. administered with meals for 7 days. Cure was tested by either endoscopy or breath test after 2 months, and by urea breath test 6 months after therapy. RESULTS: Seven patients were lost to follow-up. Of the remaining 115, 110 were cured at the first control, giving an intention-to-treat cure rate of 90.2% (95% CI: 83-95%) and a per protocol cure rate of 95.7% (95% CI: 90-98%). One hundred three patients returned for a 6-month breath test; all but one were cured. Side-effects were minimal or minor in 47 patients (40.8%) and moderate in four (3.4%). Compliance was good, 95% of patients taking more than 90% of the pills. Six (5%) patients stopped treatment after 1, 2, 4 (two patients) and 6 (two patients) days. CONCLUSION: Thrice a day quadruple therapy shows excellent cure rates, far above 90%, is well-tolerated and compliance is easy. Head-to-head comparison with triple therapies as first line Helicobacter pylori treatment seems warranted.

Administration, Oral↗

Differential effects of fasting and dehydration in the pathogenesis of diabetic ketoacidosis.

Glycemia varies widely in patients with diabetic ketoacidosis (DKA), with plasma glucose concentrations between 10 to 50 mmol/L commonly encountered. The mechanism of this glycemic variability is uncertain. Our study examined the differential effects of fasting and dehydration on hyperglycemia induced by withdrawal of insulin in type 1 diabetes. To evaluate the respective roles of dehydration and fasting in the pathogenesis of DKA, 25 subjects with type 1 diabetes were studied during 5 hours of insulin withdrawal before (control) and after either 32 hours of fasting (n = 10) or dehydration of 4.1% +/- 2.0% of baseline body weight (n = 15). Samples were obtained every 30 minutes during insulin withdrawal for substrate and counterregulatory hormone levels and rates of glucose production and disposal. Fasting resulted in reduced plasma glucose concentrations compared with the control study, while dehydration resulted in increased plasma glucose concentrations compared with the control study (P < .001). Glucose production and disposal were decreased during the fasting study and increased during the dehydration study compared with the control study. Glucagon concentrations and rates of development of ketosis and metabolic acidosis were increased during both fasting and dehydration compared with control. These data suggest that fasting and dehydration have differential effects on glycemia during insulin deficiency, with dehydration favoring the development of hyperglycemia and fasting resulting in reduced glucose concentrations. This finding is probably attributable to the differing effect of these conditions on endogenous glucose production, as well as to differences in substrate availability and counterregulatory hormone concentrations. The severity of pre-existing fasting and dehydration likely explains much of the variability in plasma glucose concentrations observed in DKA.

Adult↗

Methylotrophic Methylobacterium bacteria nodulate and fix nitrogen in symbiosis with legumes.

Rhizobia described so far belong to three distinct phylogenetic branches within the alpha-2 subclass of Proteobacteria. Here we report the discovery of a fourth rhizobial branch involving bacteria of the Methylobacterium genus. Rhizobia isolated from Crotalaria legumes were assigned to a new species, "Methylobacterium nodulans," within the Methylobacterium genus on the basis of 16S ribosomal DNA analyses. We demonstrated that these rhizobia facultatively grow on methanol, which is a characteristic of Methylobacterium spp. but a unique feature among rhizobia. Genes encoding two key enzymes of methylotrophy and nodulation, the mxaF gene, encoding the alpha subunit of the methanol dehydrogenase, and the nodA gene, encoding an acyltransferase involved in Nod factor biosynthesis, were sequenced for the type strain, ORS2060. Plant tests and nodA amplification assays showed that "M. nodulans" is the only nodulating Methylobacterium sp. identified so far. Phylogenetic sequence analysis showed that "M. nodulans" NodA is closely related to Bradyrhizobium NodA, suggesting that this gene was acquired by horizontal gene transfer.

Acyltransferases↗

Systemic and portal hemodynamic effects of anandamide.

The endogenous cannabinoid anandamide causes hypotension and mesenteric arteriolar dilation. A detailed analysis of its effects on systemic and portal venous hemodynamics had not yet been performed. We assessed the effects of anandamide (0.4-10 mg/kg) on systemic and portal hemodynamics with and without prior treatment with various antagonists. The specific antagonists used included SR-141716A, N(omega)-nitro-L-arginine methyl ester, indomethacin, and nordihydroguaiaretic acid. Anandamide produced a dose-dependent decrease in mean arterial pressure due to a drop in systemic vascular resistance (SVR) that was accompanied by a compensatory rise in cardiac output. Anandamide also elicited an increase in both portal venous flow and pressure, along with a decline in mesenteric vascular resistance (MVR). Pretreatment with 3 mg/kg SR-141716A, a CB(1) antagonist, prevented the decline of SVR and MVR from the lower dose of anandamide. Antagonism of nitric oxide synthetase, cyclooxygenase, or 5-lipoxygenase did not prevent the systemic nor the portal hemodynamic effects of anandamide. Furthermore, the use of R-methanandamide, a stable analog of anandamide, produced similar hemodynamic effects on the mesenteric vasculature, thereby implying that the effects of anandamide are not related to its breakdown products. Anandamide produced profound, dose-dependent alterations in both the systemic and portal circulations that could be at least partially blocked by pretreatment with SR-141716A.

Animals↗

Minimizing ascites. Complication of cirrhosis signals clinical deterioration.

Ascites is the most common complication of cirrhosis. Its development is associated with a grave prognosis; 50% of patients die within 2 years of diagnosis. An understanding of the analysis of ascitic fluid is essential for the appropriate management of patients with liver disease and ascites. The management of patients with ascites involves a combination of dietary, medical, and surgical approaches. Furthermore, patients with ascites are at risk for ascitic fluid infections and neurohormonal dysregulation that can lead to hepatorenal syndrome. Early recognition of these complications allows therapeutic interventions that minimize further clinical deterioration in already chronically ill patients.

Ascites↗

Theory and experiments on elastic band gaps

We study elastic band gaps in nonhomogeneous periodic finite media. The finite-difference time-domain method is used for the first time in the field of elastic band-gap materials. It is used to interpret experimental data for two-dimensional systems consisting of cylinders of fluids (Hg, air, and oil) inserted periodically in a finite slab of aluminum host. The method provides good convergence, can be applied to realistic finite composite slabs, even to composites with a huge contrast in the elastic parameters of their components, and describes well the experiments.

Journal Article↗

Ultrastructural study of the boar seminiferous epithelium: changes in cryptorchidism.

The present study compares the ultrastructural features of Sertoli cells and germ cells between scrotal testes of healthy boars and abdominal testes of unilateral and bilateral cryptorchid boars. In healthy boars, spermatogonia are flat cells lying in close association with the basal lamina. As differentiation progresses, spermatogonia acquire an oval profile and lose their contact with the basal lamina. Spermatocytes are round cells moving from the basal compartment of the seminiferous epithelium to the luminal compartment. Spermatids exhibit complex morphological changes leading to the formation of spermatozoa. Sertoli cells extend from the basal lamina to the tubular lumen. The nucleus encloses fine euchromatin and one or two nucleoli; the nuclear envelope has a few deep infoldings. The lateral cell membranes form junctional specializations that constitute the blood-testis barrier. The cytoplasm encloses smooth endoplasmic reticulum, vesicles, aggregates, and scattered mitochondria. The seminiferous epithelium of abdominal testes from unilateral and bilateral cryptorchid boars contains few spermatogonia with an abnormal appearance; the alteration in germ cell number is more severe in the bilateral disease. In unilateral cryptorchid boars, spermatogonia appear as either large pyramidal cells or roundish cells; in bilateral cryptorchid boars, spermatogonia show roundish profiles and degenerative patterns. Abdominal testes of both unilateral and bilateral cryptorchid boars are constituted by immature Sertoli cells that show abnormal cytoplasmic content, defective development of the blood-testis barrier, and atypical nuclear appearance; in bilateral cryptorchid boars, immature Sertoli cells exhibit degenerative signs. At postpubertal age, unilateral and bilateral cryptorchidism induce total arrest of spermatogenesis at spermatogonial stage as a result of an abnormal differentiation of the Sertoli cells. Moreover, the degeneration of abdominal testes initiates earlier in bilateral cryptorchidism than in unilateral cryptorchidism.

Animals↗

Combination therapy with interferon-alpha plus N-acetyl cysteine for chronic hepatitis C: a placebo controlled double-blind multicentre study.

A small pilot study in patients with chronic hepatitis C (HCV) infection suggested that antiviral treatment with interferon (IFN) plus N-acetyl cysteine (NAC) was more effective than treatment with interferon alone [Beloqui et al. (1993) Journal of Interferon Research 13:279-282]. An attempt was made to confirm this by performing a placebo-controlled double-blind study at 8 medical centres in Spain and Italy. One-hundred forty-seven patients with chronic HCV infection were investigated, 73 received 3MU IFN-alpha thrice weekly plus NAC 1800 mg daily and 74 received IFN alone. Treatment was continued for 6 months and patients were followed up for a further 6 months. Amongst patients receiving IFN plus NAC, sustained virological responses were observed in 5.5%, transient responses in 26% and non-response in 68.5%. The figures for patients receiving IFN only were 4.1%, 24.3% and 71.6% respectively. Sustained virological response was significantly associated with non-type 1 genotypes (P = 0.045) and with low pre-treatment viraemia levels (P = 0.034). Biochemical response (serum ALT concentrations) correlated with virological outcome in 97% (n = 139) of cases. Patients who experienced a sustained virological response also showed reduction in the Knodell histological activity index. It is concluded that patients with chronic HCV infection are very unlikely to benefit from the addition of N-acetyl cysteine to conventional therapy with interferon-alpha.

Acetylcysteine↗

Effects of intermittent hypoxia on the isocapnic hypoxic ventilatory response and erythropoiesis in humans.

Isocapnic hypoxic ventilatory response (HVR) and hematological variables were measured in nine adult males (age: 29.3+/-3.4) exposed to normobaric intermittent hypoxia (IH, 2 h daily at FI(O(2))=0.13, equivalent to 3800 m altitude) for 12 days. Mean HVR significantly increased during IH, however, after reaching a peak on Day 5 (0.79+/-0.12 vs. 0.27+/-0.11 L.min(-1).%(-1) on Day 1, P<0.05), it progressively decreased toward a lower value (0.46+/-0.16 L min(-1) x %(-1) on Day 12). In contrast, the subjects showed no changes in the ventilatory data and arterial O(2)-saturation in normoxia or poikilocapnic hypoxia (PET(CO(2)) uncontrolled). Hematocrit and hemoglobin concentration did not change, but the reticulocyte count increased by Day 5 (P<0.01). Our results suggest that moderate intermittent hypoxia induces changes in ventilatory O(2)-sensitivity and triggers the hematological acclimatization by increasing the percentage of reticulocytes in the blood. Normal ventilatory acclimatization to hypoxia was, however, not observed and the mechanisms involved in the biphasic changes in HVR we observed remain to be determined.

Adult↗

Effect of protective agents, rehydration media and initial cell concentration on viability of Pantoea agglomerans strain CPA-2 subjected to freeze-drying.

The effect of initial cell density, protective agents and rehydration media on the viability of biocontrol agent Pantoea agglomerans CPA-2 when subjected to freeze-drying was studied. Several additives were tested as protective agents against freeze-drying injury. Maximum viability of the bacterial cells was obtained with disaccharides (survival levels > 60%). Freeze-dried samples were rehydrated with several media; the highest percentage viability was obtained with 10% non-fat skim milk (100%+). The effect of initial bacterial load on the final recovery was dependent on protectant but not on rehydration media. Sucrose was an effective protectant when a high initial concentration (10(10) cfu ml(-1) was used; the opposite occurred with non-fat skim milk. The use of 10(10) cfu ml(-1) as an initial concentration, sucrose as a protectant and non-fat skim milk as a rehydration medium enabled 100% of P. agglomerans viability to be conserved after freeze-drying. Results suggest the possibility of achieving a good formulation system for the studied biocontrol agent with a high number of viable cells to be used toward pathogens, which is desirable for the industrial development of the product.

Animals↗

Physiological effects of intermittent hypoxia.

Intermittent hypoxia (IH), or periodic exposure to hypoxia interrupted by return to normoxia or less hypoxic conditions, occurs in many circumstances. In high altitude mountaineering, IH is used to optimize acclimatization although laboratory studies have not generally revealed physiologically significant benefits. IH enhances athletic performance at sea level if blood oxygen capacity increases and the usual level of training is not decreased significantly. IH for high altitude workers who commute from low altitude homes is of considerable practical interest and the ideal commuting schedule for physical and mental performance is being studied. The effect of oxygen enrichment at altitude (i.e., intermittent normoxia on a background of chronic hypoxia) on human performance is under study also. Physiological mechanisms of IH, and specifically the differences between effects of IH and acute or chronic continuous hypoxia remains to be determined. Biomedical researchers are defining the molecular and cellular mechanisms for effects of hypoxia on the body in health and disease. A comparative approach may provide additional insight about the biological significance of these effects.

Acclimatization↗

Limited usefulness of a seven-day twice-a-day quadruple therapy.

OBJECTIVE: To test the usefulness of a twice-a-day, simplified quadruple therapy to cure Helicobacter pylori infection. DESIGN: Helicobacter pylori-positive ulcer patients were treated with omeprazole 20 mg twice a day (b.d.), amoxicillin 1 g b.d., tinidazole 500 mg b.d. and bismuth subcitrate 240 mg b.d. for 7 days in an experimental, noncomparative pilot study. SETTING: The gastroenterology unit of a county hospital. PARTICIPANTS: Forty-four consecutive patients with peptic ulcer disease and H. pylori infection. MEASUREMENTS: Cure was tested by either endoscopy or breath test after 2 months, and by urea breath test 6 months after therapy. RESULTS: One patient was lost to follow-up. Of the remaining 43, 37 were cured at the first control, giving an intention-to-treat cure rate of 84.1% (95% CI 69-93%) and a per protocol cure rate of 86% (95% CI 71-94%). Thirty-three cured patients agreed to return for a six-month breath test. All but one were cured (long-term per protocol cure rate 82.1%; 95% CI 66-92%). CONCLUSIONS: This particular quadruple therapy is well tolerated and easy to comply with. However, cure rates did not reach 90%.

Adult↗

Nature of sonoluminescence: noble gas radiation excited by hot electrons in cold water

It was proposed before that single bubble sonoluminescence (SBSL) may be caused by strong electric fields occurring in water near the surface of collapsing gas bubbles because of the flexoelectric effect involving polarization resulting from a gradient of pressure. Here we show that these fields can indeed provoke dynamic electric breakdown in a micron-size region near the bubble and consider the scenario of the SBSL. The scenario is (i) at the last stage of incomplete collapse of the bubble, the gradient of pressure in water near the bubble surface has such a value and a sign that the electric field arising from the flexoelectric effect exceeds the threshold field of the dynamic electrical breakdown of water and is directed to the bubble center; (ii) mobile electrons are generated because of thermal ionization of water molecules near the bubble surface; (iii) these electrons are accelerated in "cold" water by the strong electric fields; (iv) these hot electrons transfer noble gas atoms dissolved in water to high-energy excited states and optical transitions between these states produce SBSL UV flashes in the transparency window of water; (v) the breakdown can be repeated several times and the power and duration of the UV flash are determined by the multiplicity of the breakdowns. The SBSL spectrum is found to resemble a black-body spectrum where temperature is given by the effective temperature of the hot electrons. The pulse energy and some other characteristics of the SBSL are found to be in agreement with the experimental data when realistic estimates are made.

Journal Article↗

Isolation and characterization of canthaxanthin biosynthesis genes from the photosynthetic bacterium Bradyrhizobium sp. strain ORS278.

A carotenoid biosynthesis gene cluster involved in canthaxanthin production was isolated from the photosynthetic Bradyrhizobium sp. strain ORS278. This cluster includes five genes identified as crtE, crtY, crtI, crtB, and crtW that are organized in at least two operons. The functional assignment of each open reading frame was confirmed by complementation studies.

Alkyl and Aryl Transferases↗

Topological differences along mammalian motor nerve terminals for spontaneous and alpha-bungarotoxin-induced sprouting.

Spontaneous sproutings can be observed in end plates from normal adult vertebrate muscles and motor end plates develop increased growth signs and sprouts when target muscle cells become less active or paralysed. Nevertheless, very little is known about where in the motor nerve terminal arborization spontaneous and experimentally induced sprouts originate, their similarities and differences and also about their final maturation or elimination. In this study we investigate the topological properties of both spontaneous and alpha-bungarotoxin-induced sprouts (during different periods of intoxication and after recovery) along the motor nerve terminal branches of the Levator auris longus muscle of Swiss mice (between 48-169 day old). Muscles were processed for immunocytochemistry to simultaneously detect postsynaptic AChRs and axons. This procedure permits us to make an accurate identification of the fine sprouts and a morphometric study of the presynaptic branching pattern profile in control muscles, during the toxin action and after recovery from paralysis. The results show that in normal muscles, the initial and trunk segments (those between branch points) of the terminal arborization sprouted proportionally more branches when taking their relative lengths into account than the distal free-end segments. In contrast, every micrometer of alpha-bungarotoxin-treated muscles throughout the full terminal arborization have the same probability of generating a sprout. Moreover, the toxin-induced sprouts can consolidate as new branches once recovered from the paralysis without changing the total length of the nerve terminal arborization.

Aging↗