Biomedical subjects
Publications and source records attributed to L Pinto.
We report a 3-year-old boy with isolated 3-methylcrotonyl-coenzyme A deficiency with unexpectedly severe presentation, seizures and history of cerebral ischae-mic episode.
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BACKGROUND: In 1998, there was a large outbreak of acute glomerulonephritis in Nova Serrana, Brazil, caused by group C Streptococcus zooepidemicus. This article reviews the characteristics of the outbreak and some aspects of the patients' follow-up. METHODS: We describe clinical characteristics of patients with acute nephritis. Using case-control studies, we identified the source of infection. Cultures of oropharyngeal swabs from patients were performed. Of 135 patients identified in 1998, available patients were reexamined in a prospective study after 2 and 5 years. RESULTS: Lancefield group C S. zooepidemicus was identified as the causative organism and linked to the consumption of cheese produced from unpasteurized milk. Of the original group of 134 patients, 4 died in the acute phase and 5 (3.7%) required chronic dialysis. After 2 years, of the 69 cases reevaluated, 94% were adults (mean +/- standard error age: 39 +/- 2 years); we found arterial hypertension in 42% (N= 27/64) of the patients, reduced creatinine clearance (<80 mL/min/1.73 m(2)) in 30% (N= 20/67), and increased microalbuminuria (>20 microg/min) in 34% (N= 22/65). Preliminary data at 5-year follow-up suggest that the percentage of patients with creatinine clearance lower than 60 mL/min increased from 9% to 15%. CONCLUSION: This article highlights the dangers of consuming unpasteurized dairy products. Follow-up of patients with epidemic poststreptococcal glomerulonephritis due to S. zooepidemicus show that a considerable proportion present hypertension, reduced renal function, and increased microalbuminuria.
STUDY OBJECTIVE: To evaluate the efficacy of, and patients' satisfaction with, office hysteroscopic treatment of benign intrauterine pathologies using 5F hysteroscopic instruments. DESIGN: Observational clinical study (Canadian Task Force classification II). SETTING: University center. PATIENTS: Four thousand eight hundred sixty-three (4863) women. INTERVENTION: Office hysteroscopy without analgesia or anesthesia. MEASUREMENTS AND MAIN RESULTS: We used 5F mechanical instruments (scissors, grasping forceps) to treat cervical and endometrial polyps ranging between 0.2 and 3.7 cm, as well as intrauterine adhesions and anatomic impediments. From 71.9% to 93.5% of women underwent the procedure without discomfort for all pathologies treated except endometrial polyps larger than the internal cervical os, for which 63.6% experienced low or moderate pain. At 3-month follow-up, pathology persisted in 364 patients (5.6%). CONCLUSION: Simple instruments enable us to perform many operative procedures in an office setting with excellent patient satisfaction, provided that the indications are correct.
Two ethanolic propolis extracts (EPE) with and without the caffeic acid phenethyl ester (CAPE), CAPE and galangin (major components of propolis) were investigated for anti-inflammatory activity in rats using carrageenin foot oedema, carrageenin pleurisy and adjuvant arthritis. In our experiments, EPE with CAPE and CAPE alone significantly inhibited carrageenin oedema, carrageenin pleurisy and adjuvant arthritis. In contrast EPE without CAPE and galangin did not exhibit anti-inflammatory effects in acute and chronic inflammation. These results suggest that the anti-inflammatory activity of propolis is due to CAPE.
Incubation of acyclovir-resistant herpes simplex virus type 1 (ACVr-HSV1), during infection of the HEp-2 cell culture, with an extract prepared from the seeds of Licania tomentosa (Benth.) Fritsch (Chrysobalanaceae) species impaired the productive replication of this virus in a concentration-dependent manner. The extract was able to inhibit extracellular virus (virucidal effect) and also interfered with a very early event of cell infection, at a non-cytotoxic concentration.
We recently reported a significant relationship between tumor cell expression of the ERBB4 receptor, the most recently described member of the epidermal growth factor receptor family, and aggressive tumor phenotype in childhood medulloblastoma. Two alternative juxtamembrane (JM) isoforms of the ERBB4 receptor have been described. Termed JMa and JMb, these variants possess different receptor processing and ligand-binding characteristics. In the current study, we employed an RT-PCR and sequencing strategy to determine the pattern of ERBB4 JM isoform expression in a large (n = 78) series of pediatric medulloblastomas. JMa and JMb transcript expression was detected in 53% and 28% of tumor samples, respectively. In addition, two novel ERBB4 JM isoforms, which we have termed JMc and JMd, were isolated from 10% and 36% of tumors, respectively. Sequence analysis revealed the JMc transcript to contain a deletion of the entire JM region. In contrast, JMd includes an extended coding region, retaining both the JMa and JMb sequences. Neither of these novel isoforms was detected in normal human adult cerebellum, but expression of JMd was observed in developing fetal cerebellum, suggesting that this later isoform may represent an ERBB4 transcript restricted to primitive neuroectoderm-derived tissue. To confirm that the four ERBB4 JM isoforms arise by alternative RNA splicing, we sequenced the intron-exon junctions of the human ERBB4 gene within the JM region. This demonstrated the four ERBB4 JM variants to be encoded by two short exons containing the JMb and JMa sequences positioned in the order 5' to 3' and separated by a 121 bp intron.
This study was undertaken to evaluate the acute effects of single low doses of melatonin given to healthy volunteers in the evening. Six healthy male volunteers (age range 22-24 years) participated in this study, after signing an informed consent form. They received in a double-blind fashion placebo or 0.3 or 1.0 mg melatonin at three fixed times: 18:00, 20:00, and 21:00 hr. Polysomnographic recordings began immediately thereafter, with their being allowed to sleep. Prior to each experimental session and in the following morning, subjects completed a sleep quality questionnaire, the Profile of Mood States, the Stanford Sleepiness Scale, and underwent a visual reaction test. Significant decrease on sleep latencies was found following melatonin treatment at 18:00 and 20:00 hr. In addition, melatonin tended to improve sleep efficiency and to reduce intermittent wakefulness. However, at 21:00 hr, 0.3 mg melatonin increased latency to sleep onset and 1.0 mg melatonin had no effect on sleep variables. Furthermore, melatonin given at different times did not alter subjective sleepiness, mood, and reaction time in the following morning. The results from the present study support the notion that administration of low doses of melatonin, mimicking the nocturnal physiological concentration of this hormone may exert immediate sleep-inducing effects.
1. We have studied the effect of capsaicin, piperine and anandamide, drugs which activate vanilloid receptors and capsazepine, a vanilloid receptor antagonist, on upper gastrointestinal motility in mice. 2. Piperine (0.5 - 20 mg kg(-1) i.p.) and anandamide (0.5 - 20 mg kg(-1) i.p.), dose-dependently delayed gastrointestinal motility, while capsaicin (up to 3 mg kg(-1) i.p.) was without effect. Capsazepine (15 mg kg(-1) i.p.) neither per se affected gastrointestinal motility nor did it counteract the inhibitory effect of both piperine (10 mg kg(-1)) and anandamide (10 mg kg(-1)). 3. A per se non effective dose of SR141716A (0.3 mg kg(-1) i.p.), a cannabinoid CB(1) receptor antagonist, counteracted the inhibitory effect of anandamide (10 mg kg(-1)) but not of piperine (10 mg kg(-1)). By contrast, the inhibitory effect of piperine (10 mg kg(-1)) but not of anandamide (10 mg kg(-1)) was strongly attenuated in capsaicin (75 mg kg(-1) in total, s.c.)-treated mice. 4. Pretreatment of mice with N(G)-nitro-L-arginine methyl ester (25 mg kg(-1) i.p.), yohimbine (1 mg kg(-1), i.p.), naloxone (2 mg kg(-1) i.p.), or hexamethonium (1 mg kg(-1) i.p.) did not modify the inhibitory effect of both piperine (10 mg kg(-1)) and anandamide (10 mg kg(-1)). 5. The present study indicates that the vanilloid ligands anandamide and piperine, but not capsaicin, can reduce upper gastrointestinal motility. The effect of piperine involves capsaicin-sensitive neurones, but not vanilloid receptors, while the effect of anandamide involves cannabinoid CB(1), but not vanilloid receptors.
1. We have studied the effect of cannabinoid agonists (CP 55,940 and cannabinol) on intestinal motility in a model of intestinal inflammation (induced by oral croton oil in mice) and measured cannabinoid receptor expression, endocannabinoids (anandamide and 2-arachidonylglycerol) and anandamide amidohydrolase activity both in physiological and pathophysiological states. 2. CP 55,940 (0.03 - 10 nmol mouse(-1)) and cannabinol (10 - 3000 nmol mouse(-1)) were more active in delaying intestinal motility in croton oil-treated mice than in control mice. These inhibitory effects were counteracted by the selective cannabinoid CB(1) receptor antagonist SR141716A (16 nmol mouse(-1)). SR141716A (1 - 300 nmol mouse(-1)), administered alone, increased intestinal motility to the same extent in both control and croton oil-treated mice. 3. Croton oil-induced intestinal inflammation was associated with an increased expression of CB(1) receptor, an unprecedented example of up-regulation of cannabinoid receptors during inflammation. 4. High levels of anandamide and 2-arachidonylglycerol were detected in the small intestine, although no differences were observed between control and croton oil-treated mice; by contrast anandamide amidohydrolase activity increased 2 fold in the inflamed small intestine. 5. It is concluded that inflammation of the gut increases the potency of cannabinoid agonists possibly by 'up-regulating' CB(1) receptor expression; in addition, endocannabinoids, whose turnover is increased in inflamed gut, might tonically inhibit intestinal motility.
From the leaf surface exudate of the aerial parts of Salvia cinnabarina a new secoisopimarane diterpenoid with a non-specific spasmolytic activity on histamine-, acetylcholine-, and barium chloride-induced contractions in the isolated guinea-pig ileum was obtained. The IC50 value obtained was comparable with that obtained for papaverine. The structure of 3,4-secoisopimara-4(18),7,15-triene-3-oic acid was established by 1D and 2D NMR spectroscopic techniques.
OBJECTIVE: Antihypertensive therapy with thiazides decreases coronary events in elderly patients. However, the influence of diuretics on myocardial ischemia has not been fully investigated. The aim of this study was to compare the effect of chlorthalidone and diltiazem on myocardial ischemia. METHODS: Following a randomized, double-blind, crossover protocol, we studied 15 elderly hypertensive patients aged 73.6+/-4.6 years with myocardial ischemia. All patients had angiographically documented coronary artery disease. We measured patients using 48- hour ambulatory electrocardiogram monitoring and exercise testing. After a 2-week period using placebo, patients received chlorthalidone or diltiazem for 4 weeks. RESULTS: Both treatments lowered systolic and diastolic blood pressures. The number of ischemic episodes on ambulatory electrocardiogram recordings was reduced with the use of chlorthalidone (2.5+/-3.8) and diltiazem (3.2+/-4.2) when compared with placebo (7.9+/-8.8; p<0.05). The total duration of ischemic episodes was reduced in both treatments when compared with placebo (chlorthalidone: 19.2+/-31.9min; diltiazem: 19.3+/-29.6min; placebo: 46.1+/-55.3min; p<0.05). CONCLUSION: In elderly hypertensive patients with coronary artery disease, chlorthalidone reduced myocardial ischemia similarly to diltiazem. This result is consistent with epidemiological studies and suggests that reduction of arterial blood pressure with thiazide therapy plays an important role in decreasing myocardial ischemia.
We have inactivated the nuclear gene coding for a putative NAD(P)H dehydrogenase from the inner membrane of Neurospora crassa mitochondria by repeat-induced point mutations. The respiratory rates of mitochondria from the resulting mutant (nde-1) were measured, using NADH or NADPH as substrates under different assay conditions. The results showed that the mutant lacks an external calcium-dependent NADPH dehydrogenase. The observation of NADH and NADPH oxidation by intact mitochondria from the nde-1 mutant suggests the existence of a second external NAD(P)H dehydrogenase. The topology of the NDE1 protein was further studied by protease accessibility, in vitro import experiments, and in silico analysis of the amino acid sequence. Taken together, it appears that most of the NDE1 protein extends into the intermembrane space in a tightly folded conformation and that it remains anchored to the inner mitochondrial membrane by an N-terminal transmembrane domain.
The extensive use of plants as medicines has pointed out that herbal medicines are not as safe as frequently claimed. Therefore, it can be harmful to take herbal medicines without being aware of their potential adverse effects. A comprehensive surveillance system for monitoring the adverse effects of herbal medicines is now essential. Also knowledge of the correlation existing between the marker compounds and other ingredients that occur in plants is a necessary requirement for ensuring the efficacy and quality of the herbal medicines.
This study examines the anti-ulcerogenic activity of eugenol, a natural compound obtained from many natural sources. Gastric ulcers, induced by administration of two ulcerogenic agents, i.e. platelet activating factor (PAF) and ethanol, were dose-dependently and significantly reduced by eugenol (10-100 mg/kg, p.o.) pre-treatment. Eugenol was able to reduce not only the number of ulcers but also the gravity of lesions.
We have evaluated the effect of cannabinoid drugs, administered intraperitoneally (i.p.) or intracerebroventricularly (i.c.v.) on upper gastrointestinal transit in control and in croton oil-treated mice. The cannabinoid agonists, WIN 55,212-2 (2-239 nmol mouse(-1)) and cannabinol (24-4027 nmol mouse(-1)), decreased while the CB(1) antagonist SR141716A (2-539 nmol mouse(-1)) increased transit in control mice. WIN 55,212-2, cannabinol and SR141716A had lower ED(50) values when administered i.c.v., than when administered i.p. The CB(2) antagonist SR144528 (52 nmol mouse(-1), i.p.) was without effect. During croton oil (0.01 ml mouse(-1), p.o.)-induced diarrhoea, the ED(50) values of i.p. -injected WIN 55,212-2 and cannabinol (but not SR141716A) were significantly decreased (compared to control mice). However, the ED(50) values of WIN 55,212-2 were similar after i.p. or i.c.v. administration. The inhibitory effects of WIN 55,212-2 and cannabinol were counteracted by SR141716A (16 nmol mouse(-1), i.p.) but not by SR144528 (52 nmol mouse(-1), i.p.) both in control and croton-oil treated mice. Ganglionic blockade with hexamethonium (69 nmol mouse(-1), i.p.) did not modify the inhibitory effect of i.p. -injected cannabinoid agonists either in control or in croton-oil treated mice. The lower ED(50) values of cannabinoid drugs after i.c.v. administration suggest a central (CB(1)) site of action. However, a peripheral site of action is suggested by the lack of effect of hexamethonium. In addition, croton oil-induced diarrhoea enhances the effect of cannabinoid agonists by a peripheral mechanism.
OBJECTIVE: To report an unusual life-threatening complication of the performance of a computed tomographic (CT) scan of the chest. DESIGN: Case report. SETTING: University hospital. PATIENT: An intubated patient with blunt thoracic trauma. INTERVENTION: Performance of a CT scan of the chest at full inspiration. MAIN RESULT: With air insufflation, a large left ventricular air embolism occurred as a consequence of an airway breach, revealed by the simultaneous existence of a mild bilateral anterior pneumothorax. CONCLUSION: CT scan of the chest in patients at risk of airway breach (patients with acute respiratory distress syndrome, trauma patients) should first be performed at full expiration, not full inspiration.