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Biomedical subjects

J Jaramillo

Publications and source records attributed to J Jaramillo.

At least 19 recordsLinked to original sources

Coffee berry borer Hypothenemus hampei (Coleoptera: Curculionidae): searching for sustainable control strategies.

The coffee berry borer Hypothenemus hampei (Ferrari) is the most serious pest of the world's most valuable tropical export crop. Since the last review on this insect was published six years ago, many new studies have contributed to an improved insight into the biology and ecology of the beetle, and have indicated new avenues for integrated and biological control. The latest developments in research, both laboratory and field, on the pest, its natural enemies and their implications for integrated control of H. hampei are summarized, with a particular focus on the situation in The Americas. Lately, the global coffee industry has changed radically; it has suffered a long cycle of lowest-ever world market prices caused by overproduction and technological change. At the same time, the advent of sustainable certification schemes has had a major impact on the industry. The role of integrated pest management and biological control of H. hampei in an era of changes in the coffee industry is discussed.

Agriculture↗

Biological control of the coffee berry borer Hypothenemus hampei (Coleoptera: Curculionidae) by Phymastichus coffea (Hymenoptera: Eulophidae) in Colombia.

The potential of the eulophid parasitoid Phymastichus coffea LaSalle to control coffee berry borer Hypothenemus hampei (Ferrari) populations under field conditions in Colombia was evaluated. Parasitoid adults were released one, five and nine days after artificial infestations of 90-, 150- and 210-day-old coffee berries with H. hampei females. The position of the beetle inside the berry and the parasitism levels were assessed ten days after each P. coffea release. Parasitism of H. hampei by P. coffea was significantly affected by the age of the berries at the time of infestation, and by the position of the beetle inside the berries. Highest levels of parasitism were recorded in 150-day-old berries (75-85%) and in 90-day-old berries (75%) when P. coffea were released one day after the artificial infestation with H. hampei. In 150-day-old berries, highest levels of parasitism were recorded for H. hampei found in the outer layer of the endosperm followed by beetles penetrating the exocarp. Increasing the time of P. coffea releases after the artificial infestations with H. hampei led to decreased levels of parasitism in beetles attacking 90- and 150-day-old coffee berries. Low levels of parasitism were recorded in H. hampei females infesting older coffee berries because most of the beetles had already constructed galleries deep in the endosperm of the berries, i.e. out of reach of the parasitoid. The potential of P. coffea for biological control of coffee berry borer in Colombia is discussed.

Animals↗

Comparison between thermal and ozone regenerations of spent activated carbon exhausted with phenol.

Thermal and ozone regenerations of granular activated carbons (GAC) used in the removal of phenol from aqueous solution have been studied. The phenol isotherms for virgin GAC could be well represented by the Langmuir equation. Direct ozonation of GAC introduced large amounts of acidic surface oxygen groups, which caused a decrease in the phenol uptake. Thermogravimetric methods were used to investigate the mechanism of phenol adsorption onto virgin and ozonated carbons. Thermal regeneration was carried out at 1123K using nitrogen (pyrolysis alone) or nitrogen and carbon dioxide (pyrolysis plus oxidation). Results showed that spent carbons do not recover their adsorption characteristics when heated under inert conditions whereas carbon dioxide regeneration was effective at about 15% wt burn-off. Regeneration of GAC was also carried out with ozone as oxidizing gas at room temperature. Ozone dose and the nature of GAC have much influence on the regeneration performance. For an individual GAC there exits an optimum ozone dose for which phenol is eliminated together with most of its oxidation by-products without incurring in carbon surface chemical alterations. However, if excessive ozone is applied some acidic surface groups are formed on the GAC, thereby decreasing the adsorption capacity for phenol. Results showed that spent carbons can recover most of their adsorption characteristics and specific surface areas when regenerated through a number of adsorption-ozone regeneration cycles.

Adsorption↗

The human renin infused rat: use as an in vivo model for the biological evaluation of human renin inhibitors.

The human renin infused rat model (HRIRM) was used as an in vivo small-animal model for evaluating the efficacy of a collection of inhibitors of human renin. The intravenous infusion of recombinant human renin (2.4 microg x kg(-1) x min(-1)) in the ganglion-blocked, nephrectomized rat produced a mean blood pressor response of 47+/-3 mm Hg (1 mm Hg = 133.3 Pa), which was reduced by captopril, enalkiren, and losartan in a dose-dependent manner following oral administration, with ED50 values of 0.3+/-0.1, 2.5+/-0.9, and 5.2+/-1.6 mg/kg, respectively. A series of peptidomimetic P2-P3 butanediamide renin inhibitors inhibited purified recombinant human renin in vitro in a concentration-dependent manner, with IC50 values ranging from 0.4 to 20 nM at pH 6.0, with a higher range of IC50 values (0.8-80 nM) observed at pH 7.4. Following i.v. administration of renin inhibitors, the pressor response to infused human renin in the HRIRM was inhibited in a dose-dependent manner, with ED50 values ranging from 4 to 600 microg/kg. The in vivo inhibition of human renin following i.v. administration in the rat correlated significantly better with the in vitro inhibition of human renin at pH 7.4 (r = 0.8) compared with pH 6.0 (r = 0.5). Oral administration of renin inhibitors also resulted in a dose-dependent inhibition of the pressor response to infused human renin, with ED50 values ranging from 0.4 to 6.0 mg/kg and the identification of six renin inhibitors with an oral potency of <1 mg/kg. The ED50 of renin inhibitors for inhibition of angiotensin I formation in vivo was highly correlated (r = 0.9) with the ED50 for inhibition of the pressor response. These results demonstrate the high potency, dose dependence, and availability following oral administration of the butanediamide series of renin inhibitors.

Administration, Oral↗

Radiofrequency catheter ablation versus medical therapy for initial treatment of supraventricular tachycardia and its impact on quality of life and healthcare costs.

We prospectively compared the impact on quality of life and cost effectiveness between ablation and medication as an initial strategy for patients with paroxysmal supraventricular tachycardia (SVT). Seventy-nine consecutive patients with newly documented paroxysmal SVT were treated with either ablation or medication. Health surveys (SF-36 and disease-specific questions) were obtained at baseline and after 12 months of follow up. Cost of health care utilization for the 6 months before and after treatment were measured. Both medication and ablation improved quality of life. However, ablation improved quality of life in more general health categories than medication. At follow up, ablation was associated with significantly improved quality of life in the bodily pain (63+/-24 vs 81+/-20, p <0.005), general health (69+/-21 vs 79+/-21, p <0.05), vitality (55+/-21 vs 66+/-22, p <0.05), and role emotion (78+/-36 vs 94+/-17, p <0.05) categories when compared with medication. Although both medication and ablation decreased frequency of disease-specific symptoms, ablation resulted in complete amelioration of symptoms in more patients (33% vs 74%). Potential long-term costs were similar for medication and ablation. In conclusion, ablation improves health-related quality of life to a greater extent, and in more aspects of general and disease-specific health than medication.

Activities of Daily Living↗

A noncompliant patient with fluctuating capacity.

Because of intermittent refusal of both dialysis and medications, serial capacity assessments were made on a 38-year-old male on hemodialysis and receiving TB treatment. His capacity to make an informed treatment decision appeared to fluctuate and despite multidisciplinary involvement and a court determination that treatment should take place, questions remained as to how such a case should be managed in the patient's best interest. The process of making a capacity determination was reviewed from both a psychiatric and legal viewpoint and alternative strategies presented.

Adult↗

Safety and efficacy of hydrogen peroxide plasma sterilization for repeated use of electrophysiology catheters.

OBJECTIVES: The purpose of this study was to evaluate a new technique for sterilizing nonlumen electrophysiology catheters that uses hydrogen peroxide gas plasma. BACKGROUND: The reuse of electrophysiology catheters may potentially result in a significant cost savings. While ethylene oxide sterilization appears to be safe and effective from a clinical standpoint, toxic ethylene oxide residuals, which exceed Food and Drug Administration standards, have been reported. METHODS: Ten nonlumen electrophysiology catheters were extensively evaluated. Each catheter was used five times and resterilized after each use with hydrogen peroxide gas plasma. Tests for sterility, mechanical and electrical integrity, chemical residuals and standard and electron microscopic inspection were performed. RESULTS: Loss of electrical integrity or mechanical integrity was not observed in any catheter. No evidence of microbial contamination was found. Surface integrity was preserved except for one ablation catheter that exhibited fraying of the insulation at the insulation-electrode interface. Surface inspection using standard magnification and electron microscopy revealed no significant change in surface characteristics associated with the sterilization process. Hydrogen peroxide was the only chemical residual noted, with an average concentration of 0.22% by weight, which is within accepted American Association for the Advancement of Medical Instrumentation limits. The cost for a standard electrophysiology catheter ranges from $200 to $800, and one sterilization cycle costs $10. If electrophysiology catheters are used five times, resterilization could potentially result in a savings of $2,000 per catheter, or $9,000 for five ablation procedures. CONCLUSIONS: Hydrogen peroxide gas plasma sterilization may provide a cost-effective means of sterilizing nonlumen electrophysiology catheters without the problem of potentially harmful chemical residuals. However, careful visual inspection of catheters, particularly at the insulation-electrode interface, is required if catheter reuse is performed.

Anti-Infective Agents, Local↗

Antiviral activity of a selective ribonucleotide reductase inhibitor against acyclovir-resistant herpes simplex virus type 1 in vivo.

The present study reports the activity of BILD 1633 SE against acyclovir (ACV)-resistant herpes simplex virus (HSV) infections in athymic nude (nu/nu) mice. BILD 1633 SE is a novel peptidomimetic inhibitor of HSV ribonucleotide reductase (RR). In vitro, it is more potent than ACV against several strains of wild-type as well as ACV-resistant HSV mutants. Its in vivo activity was tested against cutaneous viral infections in athymic nude mice infected with the ACV-resistant isolates HSV type 1 (HSV-1) dlsptk and PAAr5, which contain mutations in the viral thymidine kinase gene and the polymerase gene, respectively. Following cutaneous infection of athymic nude mice, both HSV-1 dlsptk and PAAr5 induced significant, reproducible, and persistent cutaneous lesions that lasted for more than 2 weeks. A 10-day treatment regimen with ACV given topically four times a day as a 5% cream or orally at up to 5 mg/ml in drinking water was partially effective against HSV-1 PAAr5 infection with a reduction of the area under the concentration-time curve (AUC) of 34 to 48%. The effects of ACV against HSV-1 dlsptk infection were not significant when it was administered topically and were only marginal when it was given in drinking water. Treatment under identical conditions with 5% topical BILD 1633 SE significantly reduced the cutaneous lesions caused by both HSV-1 dlsptk and PAAr5 infections. The effect of BILD 1633 SE against HSV-1 PAAr5 infections was more prominent and was inoculum and dose dependent, with AUC reductions of 96 and 67% against infections with 10(6) and 10(7) PFU per inoculation site, respectively. BILD 1633 SE also significantly decreased the lesions caused by HSV-1 dlsptk infection (28 to 51% AUC reduction). Combination therapy with topical BILD 1633 SE (5%) and ACV in drinking water (5 mg/ml) produced an antiviral effect against HSV-1 dlsptk and PAAr5 infections that was more than the sum of the effects of both drugs. This is the first report that a selective HSV RR subunit association inhibitor can be effective against ACV-resistant HSV infections in vivo.

Acyclovir↗

Cutaneously applied acyclovir acts systemically in the treatment of herpetic infection in the hairless mouse.

Using the SKH-1 hairless mouse (HM) we have addressed the issue as to whether topically applied acyclovir (ACV) may mediate some of its antiviral actions by a systemic effect. When topically applied in a formulation consisting of polyvinyl alcohol (25% w/v):DMSO:cremophor EL:linoleic acid (63:16:16:5, v/v/v/v), ACV penetrated hairless mouse skin in a concentration-dependent manner and dose-dependently reduced cutaneous herpes simplex virus 1 (HSV-1) KOS infection. Topically applied ACV also effectively reduced the mortality associated with disseminated HSV-2 HG-52 infection. At 1 h following topical application of 1.7% w/v ACV the plasma and skin concentrations of ACV were 5.5 nmoles/ml and 120 nmoles/g. At 1 h following an oral dose of ACV with antiviral efficacy comparable to topically applied ACV (1.7% w/v) the plasma and skin concentrations of ACV were 21.3 nmoles/ml and 51 nmoles/g. These findings imply that when applied topically to the HM, ACV can mediate a portion of its antiviral activity through a systemic mode of action.

Acyclovir↗

Soluble HLA class I antigens in patients with type I diabetes and their family members.

Our objective was to study a possible contribution of MHC genes to S-HLA-I secretion in patients with Type I diabetes. Quantitatively, we used a highly sensitive enzyme-linked immunoassay to measure S-HLA-I in the serum of a total of 39 patients with Type I diabetes, as well as 36 kinships of 12 diabetic patients and 82 normal individuals with known HLA-phenotypes. S-HLA-I levels were abnormally elevated in patients or their non-diabetic relatives compared to normal controls (p < 0.0009). No complete HLA-haplotype had been identified to be correlated with high or low S-HLA-I secretion. Only the HLA-A23 or A24 (splits of HLA-A9) positive individuals sera were found to contain high S-HLA-I concentrations in all populations studied. The difference in S-HLA-I levels of HLA-A24 patients (n = 4) or their HLA-A24 positive non-diabetic relatives (n = 10) to the group of HLA-A24 normal controls (n = 15) was statistically highly significant (p < 0.0005 and p < 0.0009, respectively). The results suggests that HLA-A24 may confer additional independent risk for the disease expression in male children but not in female siblings. Nevertheless, the data implies that the patients or their non-diabetic relatives carrying the HLA-A24 have increased risk of developing ICA associated with high S-HLA-I levels compared to HLA-A24 negative probands or their kinships with low levels of S-HLA-I. This effect occurred irrespective to other diabetes related HLA-DR alleles. In summary, the results show a pronounced genetic heterogeneity of Type I diabetes with MHC control of the expression of S-HLA-I and possible involvement of hormonal factors that might potentiate a specific synthesis of S-HLA-I. The findings have implications for identifying individuals with a possible risk for developing the disease.

Diabetes Mellitus, Type 1↗

A left free-wall, decrementally conducting, atrioventricular (Mahaim) fiber: diagnosis at electrophysiological study and radiofrequency catheter ablation guided by direct recording of a Mahaim potential.

A 64-year-old female with Wolff-Parkinson-White syndrome and an ECG demonstrating a right posterolateral accessory pathway was referred for electrophysiological study. During electrophysiological testing two AV pathways were identified: a right posterolateral pathway that displayed conventional electrophysiological properties: and a left free-wall pathway that conducted only anterogradely and demonstrated decremental properties. Two separate wide complex tachycardias were induced that utilized the left free-wall pathway anterogradely and either the AV node or the right posterolateral accessory pathway retrogradely. A discrete electrical potential on the free wall of the mitral annulus was identified during tachycardia and was utilized to facilitate mapping and ablation.

Atrioventricular Node↗

Peptidomimetic inhibitors of herpes simplex virus ribonucleotide reductase with improved in vivo antiviral activity.

We have been investigating the potential of a new class of antiviral compounds. These peptidomimetic derivatives prevent association of the two subunits of herpes simplex virus (HSV) ribonucleotide reductase (RR), an enzyme necessary for efficient replication of viral DNA. The compounds disclosed in this paper build on our previously published work. Structure-activity studies reveal beneficial modifications that result in improved antiviral potency in cell culture in a murine ocular model of HSV-induced keratitis. These modifications include a stereochemically defined (2,6-dimethylcyclohexyl)amino N-terminus, two ketomethylene amide bond isosteres, and a (1-ethylneopentyl)amino C-terminus. These three modifications led to the preparation of BILD 1351, our most potent antiherpetic agent containing a ureido N-terminus. Incorporation of the C-terminal modification into our inhibitor series based on a (phenylpropionyl)valine N-terminus provided BILD 1357, a significantly more potent antiviral compound than our previously published best compound, BILD 1263.

Animals↗

A novel renal hypertensive guinea pig model for comparing different inhibitors of the renin-angiotensin system.

The present study describes a novel renal hypertensive guinea pig model for comparing different inhibitors of the renin-angiotensin system (RAS). Renal hypertension was induced by a two-step procedure consisting of ligation of the left caudal renal artery and right nephrectomy. Sham-operated animals were used as controls. Arterial blood pressure and heart rate were monitored in conscious animals. Left caudal renal artery ligation and subsequent right nephrectomy led to a significant increase (32% over sham-operated controls, p < .05) in mean arterial blood pressure (MABP), 3 to 4 weeks following surgery. Renal hypertensive animals had increased urine production (from 63 +/- 8 mL/kg per day to 143 +/- 29 mL/kg per day, p < .05) and an increased incidence of proteinuria (11/13 animals had urine protein levels higher than 20 mg/kg per day). Five of the 13 renal hypertensive animals also had hematuria. On autopsy, an 83% increase in the left kidney/body weight ratio and a 37% increase in the heart/body weight ratio were observed in the renal hypertensive animals, compared to the sham-operated controls. Changes in blood pressure and heart rate were assessed before and after an intravenous bolus injection of the drug to be tested. Captopril reduced MABP in both sham-operated and renal hypertensive animals with equal efficacy (up to a maximum of 42%). In contrast, BILA 2157 BS, one of our human renin inhibitors, produced a similar maximum MABP decrease but only in renal hypertensive animals. This selective antihypertensive effect was also observed with enalkiren, another renin inhibitor. These results indicate that the renal hypertensive guinea pig is an useful model for comparing and contrasting different RAS inhibitors.

Animals↗

Muscle aspartyl protease (cathepsin D) activity: detection using a chromophoric substrate and relation to wasting in DBA/2 mice implanted with leukemic L1210 tumor cells.

The relationship between skeletal muscle aspartyl protease activity (APA) and wasting was investigated in male DBA/2 mice inoculated with L1210 tumor cells. Using the peptidic substrate H-Pro-Thr-Glu-Phe-Phe(NO2)-Arg-Leu-OH, which is specific for aspartyl proteases, proteases, proteolytic activity was detected in a number of tissues including muscle by using a crude extraction procedure for isolation of lysosomal enzymes. Biochemical characterization and increased muscle levels following either fasting or injection of endotoxin (ETX) suggest that the enzyme is likely cathepsin D. The wasting syndrome accompanying the tumor was measured by comparing the weight of the skinned hind limb in treated and control animals. DBA/2 mice inoculated intraperitoneally with L1210 cells developed multiple solid tumors in the peritoneum and ascites; maximal tumor burden was reached by 16 days. There was a significant reduction in hind limb weight (16 +/- 2%; mean +/- SE) and significant increase (31 +/- 8%) in muscle APA associated with the development of ascites and solid tumors. Plasma APA activity was substantially increased (240 +/- 33%), while liver and spleen APA were increased (10-20%) but not significantly. Chronic pepstatin administration, 30 mg.kg-1.day-1, for 7 days concurrent with the initiation of observable ascites and solid tumor formation (7 days post-inoculation), completely inhibited hind limb weight loss and alleviated the tumor-dependent increase of APA in both plasma and muscle without altering tumor development. Delaying the administration of pepstatin by 3 days resulted in less of an inhibition (33 +/- 13%) of hind limb weight loss. Thus, cathepsin D or a similar aspartyl protease appears to be of key importance in the wasting syndrome associated with cachexia.

Animals↗

Comparative studies on differential inhibition of the renin - angiotensin system in the anesthetized guinea pig.

The present study compares the hemodynamic effects and mechanisms of action of angiotensin II (AngII) antagonists, angiotensin converting enzyme (ACE) inhibitors, and renin inhibitors in the guinea pig, an animal with high similarity to primates in terms of in vitro and in vivo responses to several human renin inhibitors. Animals were anesthetized with urethane and ketamine. The carotid artery was catheterized for monitoring blood pressure and heart rate. After 30 min stabilization, drug (or vehicle) effects were monitored for 1 h following each increasing dose (i.v. bolus injection). Drugs tested include losartan, an AngII receptor antagonist; two renin inhibitors, BILA 2157 BS and PD-134672; and captopril, an ACE inhibitor. All drugs dose dependently decreased blood pressure. Diastolic blood pressure was reduced more than systolic blood pressure, suggestive of vasodilation. The maximum decrease (32 +/- 6%, p < 0.05 vs. vehicle) in mean arterial blood pressure (MABP) by losartan was achieved with a dose of 1 mg/kg. A similar decrease in MABP was observed with renin inhibitors at a dose of 3 mg/kg, without affecting heart rate. A further increase in the dose of renin inhibitors (6 mg/kg) decreased not only blood pressure but also heart rate. Captopril decreased MABP with a maximum of 48 +/- 3% (p < 0.05 vs. vehicle, losartan, and PD-134672). In the presence of HOE-140, a bradykinin antagonist, the MABP decrease by captopril was only 35 +/- 4%, (p < 0.05 vs. captopril alone). Bilateral nephrectomy reduced the peak MABP effect of PD-134672 by 67%, while the effects of captopril on MABP were affected to a lesser degree (57%). Therefore, captopril remains more effective in reducing MABP (p < 0.05 vs. that of PD-134672). These results suggest that renin inhibitors and AngII antagonists act more specifically on the renin - angiotensin system cascade, while captopril acts partially by a bradykinin-dependent mechanism. The small animal model described provides a novel tool for the comparative pharmacologic assessment of different renin - angiotensin system inhibitors.

Alanine↗

A potent peptidomimetic inhibitor of HSV ribonucleotide reductase with antiviral activity in vivo.

Herpes simplex viruses (HSV) types 1 and 2 encode their own ribonucleotide reductases (RNRs) (EC 1.17.4.1) to convert ribonucleoside diphosphates into the corresponding deoxyribonucleotides. Like other iron-dependent RNRs, the viral enzyme is formed by the reversible association of two distinct homodimeric subunits. The carboxy terminus of the RNR small subunit (R2) is critical for subunit association and synthetic peptides containing these amino-acid sequences selectively inhibit the viral enzyme by preventing subunit association. Increasing evidence indicates that the HSV RNR is important for virulence and reactivation from latency. Previously, we reported on the design of HSV RNR inhibitors with enhanced inhibitory potency in vitro. We now report on BILD 1263, which to our knowledge is the first HSV RNR subunit-association inhibitor with antiviral activity in vivo. This compound suppresses the replication of HSV-1, HSV-2 and acyclovir-resistant HSV strains in cell culture, and also strongly potentiates the antiviral activity of acyclovir. Most importantly, its anti-herpetic activity is shown in a murine ocular model of HSV-1-induced keratitis, providing an example of potent nonsubstrate-based antiviral agents that prevent protein-protein interactions. The unique antiviral properties of BILD 1263 may lead to the design of new strategies to treat herpesvirus infections in humans.

Amino Acid Sequence↗