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Biomedical subjects

G Mora

Publications and source records attributed to G Mora.

At least 37 records · Page 2Linked to original sources

Inhibition of transcription factor NF-kappaB by sesquiterpene lactones: a proposed molecular mechanism of action.

Many sesquiterpene lactones (SLs) possess considerable anti-inflammatory activity. They inhibit the transcription factor NF-kappaB by selectively alkylating its p65 subunit probably by reacting with cysteine residues. Here we assayed 28 sesquiterpene lactones for their ability to inhibit NF-kappaB. The majority of the potent NF-kappaB inhibitors possess two reactive centers in form of an alpha-methylene-gamma-lactone group and an alpha,beta- or alpha,beta,gamma,delta-unsaturated carbonyl group. Based on computer molecular modelling we propose a molecular mechanism of action, which is able to explain the p65 selectivity of the SLs and the observed correlation of high activity with alkylant bifunctionality. A single bifunctional SL molecule can alkylate the cysteine residue (Cys 38) in the DNA binding loop 1 (L1) and a further cysteine (Cys 120) in the nearby E' region. This cross link alters the position of tyrosine 36 and additional amino acids in such a way that their specific interactions with the DNA become impossible. We also created a model for monofunctional SLs.

Anti-Inflammatory Agents, Non-Steroidal↗

Motor neuron disease: usefulness of transcranial magnetic stimulation in improving the diagnosis.

Clinical upper motor neuron (UMN) involvement is sometimes difficult to detect in motor neuron disease (MND). For this reason we performed transcranial magnetic stimulation (TMS) to find out whether this technique may be useful in revealing signs of pyramidal tract impairment. Fifty-five MND patients, clinically divided into 22 amyotrophic lateral sclerosis (ALS), 18 ALS with probable UMN signs (ALS-PUMNS), 10 pure lower motor neuron syndrome (LMNS), and 5 progressive bulbar palsy (PBP), underwent standard TMS, recording from abductor digiti minimi and flexor allucis muscles. Prolongation of cortical motor evoked potential (MEP) latency and central conduction time (CCT) and absent MEP were considered as pathologic. ALS-PUMNS and LMNS patients were clinically reclassified after 1 year. TMS was abnormal in 95.4% of ALS, 72.2% of ALS-PUMNS, 50% of LMNS and 20% of PBP. Correlations between TMS parameters and both clinical signs of UMN involvement and disease severity were highly significant. TMS showed a high sensitivity, but lacked specificity. After 1 year, 11 patients among the ALS-PUMNS group were clinically reclassified as definite ALS: all of them had shown TMS abnormalities at the first examination. In conclusion, TMS provides important diagnostic information for an early prediction of ALS in those MND patients presenting with clinically equivocal UMN impairment.

Adult↗

Sources of Vibrio mimicus contamination of turtle eggs.

Vibrio mimicus contamination of sand increased significantly during the arrival of the olive ridley sea turtles (Lepidochelys olivacea) at Ostional anidation beach, Costa Rica. Statistical analysis supports that eggs are contaminated with V. mimicus by contact with the sand nest. V. mimicus was isolated from eggs of all nests tested, and ctxA+ strains were found in 31% of the nests, all of which were near the estuary.

Animals↗

Anti-inflammatory activity of Urera baccifera (Urticaceae) in Sprague-Dawley rats.

On a preliminary test, anti-inflammatory and analgesic dose-related activities on rats were observed for the aqueous fraction of Urera baccifera; this extract was bioassay-guided fractionated and the final aqueous fraction was used according the ethnobotanical use. Carrageenan-induced edema (n = 6), was used as an assay in the fractionating process. The anti-inflammatory and antinociceptive properties of the final aqueous fraction were studied using in vivo models. For the anti-inflammatory activity rat paw edema (n = 6), pleurisy induced by carrageenan (n = 6) and ear edema induced by topical croton oil (n = 6) models were used, and tail-flick test (n = 6), abdominal constrictions induced by acetic acid (n = 6), and formalin test (n = 6), were used for the antinociceptive activity. The tests performed showed an inhibition effect on leukocyte migration, and a reduction on pleural exudate, as well as dose-dependant peripheral analgesic activity, at a range of 25-100 mg/kg i.p. The final aqueous fraction contains most of the anti-inflammatory activity of the plant U. baccifera. A possible mechanism of action is discussed and based on the results we conclude that this plant has a potential for both anti-inflammatory and analgesic activity at the clinical level.

Abdominal Muscles↗

Anti-inflammatory activity of aqueous extracts of five Costa Rican medicinal plants in Sprague-Dawley rats.

The anti-inflammatory properties of Loasa speciosa and Loasa triphylla (Loasaceae), Urtica leptuphylla and Urera baccifera (Urticaceae), and Chaptalia nutans (Asteracene) were studied using the carregeenan induced rat paw edema model. Aqueous extracts of each plant were made according to the ethnobotanical use. The hippocratic assay was made with female rats; the dose used was 500 mg/kg i.p. and the control group received 0.5 ml of n.s.s.. All the animals treated showed hypothermia, and those treated with the extracts of Chaptalia nutans, Urera baccifera and Urtica leptuphylla showed an increased colinergic activity. Acute toxicities of the aqueous extracts were studied in mice an the mean lethal doses ranged between 1.0226 and 1.2022 g/kg. The extracts of Urera baccifera, Chaptalia nutans, Loasa speciosa and Loasa triphylla (500 mg/kg i.p.) showed an anti-inflammatory activity comparable with that of indomethacin. The extracts of U. baccifera and C. nutans, which showed the greatest anti-inflammatory activity, did not show it when used orally (500 mg/kg p.o.).

Animals↗

Comparison of the modified biophysical profile to a "new" biophysical profile incorporating the middle cerebral artery to umbilical artery velocity flow systolic/diastolic ratio.

OBJECTIVES: The objective of this study was to determine whether the addition of the middle cerebral to umbilical artery systolic/diastolic velocity waveform ratio to the modified biophysical profile would improve perinatal outcome in patients at high risk. STUDY DESIGN: A prospective, randomized outcome study of patients referred to the perinatal laboratory for antenatal surveillance was undertaken. Six hundred sixty-five patients were randomized to two antenatal surveillance protocols: group 1, modified biophysical profile; and group 2, modified biophysical profile plus evaluation of the middle cerebral artery to umbilical artery systolic/diastolic ratio. Patients were followed up serially and neonatal outcome data including gestational age at delivery, birth weight, incidence of cesarean section delivery for fetal distress, admission to the neonatal intensive care unit, days in the neonatal intensive care unit, and the presence of significant neonatal morbidity were tabulated. RESULTS: The total population showed no statistical difference in outcome parameters between groups 1 and 2. However, a subgroup of patients evaluated for suspected uteroplacental insufficiency did show a significant reduction in caesarean section for fetal distress in group 2 patients. CONCLUSIONS: In a subgroup of patients at risk for uteroplacental insufficiency, the addition of the middle cerebral/umbilical artery ratio to an antenatal surveillance protocol should be expected to improve perinatal outcome.

Adult↗

The natural history and the effects of gabapentin in amyotrophic lateral sclerosis.

Glutamate excitotoxicity seems to play an important role in the aetiopathogenesis and progression of Amyotrophic Lateral Sclerosis (ALS). Gabapentin is a modulator of the glutamatergic system and has been shown to prolong survival in the transgenic model of familial ALS. It has also been demonstrated to slow the decline of arm strength in human sporadic cases. The aim of our study was to assess the effects of different dosages and duration of treatment of gabapentin on the natural history and survival of ALS patients. A total of 110 patients affected by definite ALS entered the study. After a 6-12 month period of observation, patients were randomly assigned to receive oral gabapentin 500 mg/day (Group A) or 1000 mg/day (Group B) for 6 months. In addition a group of patients received gabapentin 500 mg/day for 6 months and 1000 mg/day for a further 6 months (Group C). A group of 121 patients referred to our Institute, who received only symptomatic treatment, was considered as the control group (Group D). Each patient was seen at entry and every 3 months. All average slopes were negative but the comparison of all slopes showed a trend toward a slower rate of decline of muscle strength loss in all treated groups of patients compared with the control group. The differences were statistically significant. Analysis between the pretreatment and treatment period showed a statistically significant decrease of the decline of muscle strength and Norris score during the treatment period. Survival analysis showed a significantly longer survival in treated patients of Groups B and C. Our study suggests that gabapentin may be an effective drug for ALS; hence a controlled trial involving a sufficient large number of patients is warranted.

Acetates↗

The role of priority programmes in the provision of health services in the state of Oaxaca, Mexico.

An assessment of the performance of five priority health programmes (basic sanitation, tuberculosis, vaccination, acute respiratory infections and acute diarrheal diseases) was carried out using ethnographic techniques in the region of La Cañada in the state of Oaxaca, Mexico. The region presents a large percentage of Indian and peasant population living in extreme poverty and health care is mainly provided by the Ministry of Health. Both characteristics of the population and the health services are used to analyze the performance of the programmes. With access to abundant resources, vaccination and diarrheal disease programmes have been highly successful in involving the population and achieving their operative targets. Consequently this capacity to concentrate resources results in a lack of resources for other programmes. Despite partial successes, all programmes face serious operational difficulties demonstrating, in turn, the lack of capacity of health services to respond to the specific demands of local populations. The information presented is relevant for the discussion of selective versus comprehensive PHC.

Diarrhea↗

Study of three sesquiterpene lactones from Tithonia diversifolia on their anti-inflammatory activity using the transcription factor NF-kappa B and enzymes of the arachidonic acid pathway as targets.

In Central America leaf extracts from the Asteraceae Tithonia diversifolia are used externally for the treatment of haematomas and wounds. Therefore, the main sesquiterpene lactones (Sls) of this species growing in Costa Rica, diversifolin (1), diversifolin methyl ether (2), and tirotundin (3), were studied for their anti-inflammatory activity. We determined whether these compounds inhibit cyclooxygenase-I, phospholipase A2, or the transcription factor NF-kappa B. Here we show that these Sls do not influence the enzymes of the arachidonic acid pathway, but inhibit the activation of NF-kappa B. Thereby, the synthesis of inflammatory mediators such as cytokines and chemokines is reduced. Our results indicate that the inhibitory activity of compounds 1-3 is due to alkylation of cysteine residues, which are probably located in the DNA binding domain of NF-kappa B. The Sls were also studied for their antibacterial activity, but only Sl 1 was moderately active against Bacillus subtilis in the agar plate diffusion test.

Anti-Inflammatory Agents, Non-Steroidal↗

Deterioration of multifocal motor neuropathy after plasma exchange.

We report a patient with motor neuropathy in whom plasma exchange (PE) was followed by a pronounced clinical worsening with the appearance of conduction blocks in previously clinically unaffected motor nerves, leading to the diagnosis of multifocal motor neuropathy (MMN). This report highlights the different response to therapy of MMN and chronic inflammatory demyelinating polyneuropathy (CIDP) because not only steroids but also PE, which is often effective in CIDP, do not improve and at times may even worsen MMN.

Humans↗

A randomized comparison between misoprostol and dinoprostone for cervical ripening and labor induction in patients with unfavorable cervices.

OBJECTIVE: To compare the efficacy and safety of two prostaglandin derivatives, misoprostol and dinoprostone, for ripening the cervix and inducing labor in women with an unfavorable cervix. METHODS: One hundred fifty-five women admitted for induction of labor to St. John's Mercy Medical Center, a teaching community hospital, were randomized to one of two methods: intravaginal misoprostol, 50 microg every 4 hours up to three doses (n = 76); and intracervical dinoprostone gel, 0.5 mg every 6 hours up to three doses (n = 79). RESULTS: Misoprostol was more effective than dinoprostone in causing cervical ripening (P = .01), inducing labor (P < .001), shortening the duration of labor (P < .001), and decreasing the need for oxytocin augmentation (P < .001). Nonreassuring fetal heart monitoring patterns associated with hyperstimulation were significantly more frequent (P < .001), and the incidence of cesarean deliveries because of this indication was significantly higher (P = .002) in patients receiving misoprostol. CONCLUSIONS: Misoprostol is an effective agent for cervical ripening and labor induction, but it causes an increase in cesarean deliveries associated with uterine hyperstimulation.

Adult↗

Measurement of bone lengthening forces; an experimental model in the lamb.

OBJECTIVE: To obtain the mechanical behaviour pattern of the lengthening process. DESIGN. IN VIVO: measurement of forces during bone lengthening in lambs. BACKGROUND: A series of parameters of a mechanical and biological nature have a bearing on all lengthening processes, and most of them are not fully understood. METHODS: A strain-gauge-monitored unilateral fixator was designed and used to obtain data about the changes which took place in the forces of elongation at a rate of 1 mm/day in four lambs while a 3 cm progressive lengthening of the left tibia was being performed, analysing how these forces behaved from day to day, and how they changed in the course of a single day. RESULTS: The maximum forces in all the animals each day occur after distraction, and the forces reach their greatest magnitude between days 21 and 25 after surgery, attaining values of slightly over 8 kg (40-50% of the animal's weight). The maximum daily force starts to drop 1 h after distraction, and continues to decrease gradually throughout the day until it reaches a value slightly greater than the initial force on the previous day. CONCLUSION: This pattern is due to the distraction of soft tissues which gradually adapt to their new situation, thereby reducing the level of stress. RELEVANCE: In the daily bone lengthening procedure, the greatest forces are produced in a short period of time immediately after lengthening. they could be reduced to decrease pain in the patient and loads on the device by performing lengthening over a greater number of steps or using dynamic equipment able to absorb these forces.

Journal Article↗

Traumatic lumbosacral dislocation in a 5-year-old boy with eight years follow-up.

STUDY DESIGN: The authors present an unusual case of pure traumatic bilateral lumbosacral dislocation in a 5-year-old boy, the conservative treatment carried out, and the long-term result. OBJECTIVES: To describe a rare traumatic lesion in children and evaluate the result obtained with conservative treatment. SUMMARY OF BACKGROUND DATA: Watson-Jones was the first to describe this type of lesion. Since then, only a few cases have been added. Most authors suggest that open reduction should be carried out. No cases of this type of injury in children have been reported. METHODS: A 5-year-old boy was hit in the lumbosacral region with a rocking chair. Examination showed neurologic deficit of left L5 and S1 nerve roots. Roentgenographic examination and computed tomography scan confirmed the anterior dislocation of the fifth lumbar vertebra on the sacrum without any fracture. He was treated with traction, followed by hyperextension in a Cotrel traction table and further immobilization with a lumbar plaster jacket. RESULTS: Eight years after the injury, the patient had no neurologic deficit and lumbar radiographs showed a good alignment of the lumbosacral spine. CONCLUSION: In children with traumatic lumbosacral dislocation, closed reduction should be attempted even if neurologic deficit is present.

Child, Preschool↗

Consolidation of massive bone allografts in limb-preserving operations for bone tumours.

This study analysed the influence of several factors affecting the consolidation time of 83 massive bone allografts in 79 patients with malignant bone tumours: osteosarcoma 57; Ewing's sarcoma 8; malignant fibrous histiocytoma 3; chondrosarcoma 4; fibrosarcoma 5; and giant cell tumours 2. The mean age of the patients was 19 years and the mean length of the allografts was 18 cm. The minimum follow up was for 12 months. The mean consolidation time for metaphyseal and diaphyseal osteotomies was 6.5 and 16 months respectively. Fifteen diaphyseal osteotomies required autologous cancellous grafting. There were 8 allograft fractures after consolidation. The following factors which might influence consolidation were analysed: age of the host and donor; allograft length and site; type of osteotomy and osteosynthesis; intra-arterial and systemic chemotherapy; intraoperative and external radio-therapy. In diaphyseal osteotomies there were statistically significant differences in consolidation time with the use of systemic chemotherapy, external radiotherapy and the recipient's age.

Adolescent↗

Percutaneous endoscopic gastrostomy and enteral nutrition in amyotrophic lateral sclerosis.

Bulbar involvement in amyotrophic lateral sclerosis (ALS) is often related to a worse prognosis on account of the higher risk of pulmonary aspiration and undernutrition due to dysphagia. The aim of our study was to assess the effects of enteral feeding by percutaneous endoscopic gastrostomy (PEG) in a long-term follow-up of ALS patients. We report the results of PEG in 31 ALS patients with bulbar involvement. The patients were observed at 3-monthly intervals over a period of 2 years after PEG. All the data were compared with those obtained from a control group of 35 ALS patients who refused PEG. Mortality did not differ significantly between the two groups of patients during the first 6 months of observation, whereas after this period it was lower in the PEG group. In the patients who had had PEG, the body mass index showed a mild but statistically significant improvement after tube insertion while in the control group it decreased significantly. The findings of this study demonstrate that PEG can improve survival in elderly and young ALS patients with bulbar involvement; it enhances their quality of life and helps their integration in their social and family surroundings. We think that PEG should be included symptomatic treatment of all ALS patients with bulbar involvement from the onset of symptoms.

Adult↗

Regulation of vascular smooth muscle soluble guanylate cyclase activity, mRNA, and protein levels by cAMP-elevating agents.

Although the biochemical properties of soluble guanylate cyclase (sGC) have been extensively studied, little is known about the regulation of gene expression of sGC subunits by second messengers. cAMP analogues and elevating agents have been previously shown to alter gene expression in vascular cells. The aim of the present study was to investigate the effects of cAMP-elevating agents on sodium nitroprusside-stimulated sGC activity and to correlate activity changes with mRNA and protein levels in cultured rat aortic smooth muscle cells. Pretreatment of cells with 50 to 1000 mumol/L isobutylmethyl-xanthine or 0.01 to 10 mumol/L forskolin led to a time- and concentration-dependent decrease in sodium nitroprusside-induced cGMP accumulation, first evident after 3 hours of pretreatment with forskolin and 6 hours of pretreatment with isobutylmethylxanthine. Incubation of cells with a protein kinase A-selective inhibitor (H89 or KT 5720) partially or fully prevented the downregulation in sodium nitroprusside-induced cGMP accumulation caused by cAMP-elevating agents. Quantification of reverse transcriptase-polymerase chain reaction products by high-performance liquid chromatography revealed that mRNA for both alpha1- and beta1-subunits of sGC were decreased in cells pretreated with isobutylmethylxanthine and forskolin but not with dideoxyforskolin (inactive analogue). Moreover, protein levels for the sGC alpha1 subunit of cells pretreated with isobutylmethylxanthine and forskolin but not with dideoxyforskolin were decreased as indicated by Western blot analysis. These data indicate that cAMP-elevating agents decrease sGC activity, possibly by decreasing mRNA or protein levels or both.

Animals↗