Interactions between alcohol and gastric metabolizing enzymes: practical implications.

It has been demonstrated recently that some portion of ingested alcohol does not enter the systemic circulation and is not retained in the gastrointestinal tract; instead, gastric oxidation or first-pass metabolism of ethanol occurs in the stomach, catalyzed by gastric alcohol dehydrogenase. First-pass metabolism of ethanol is minimal in the fasting state; it is lower in women than in men, and in alcoholics than in nonalcoholics; and it is abolished in patients after subtotal gastrectomy. In addition, some drugs may affect first-pass ethanol metabolism. Studies of the effects of H2-receptor antagonists on blood ethanol levels are reviewed. It is concluded that some H2-receptor antagonists (cimetidine and nizatidine, in particular) can inhibit gastric ethanol oxidation and thus increase blood alcohol levels after drinking. The clinical and medicolegal implications of these findings are discussed.     

Grafts of porcine intestinal submucosa for repair of cervical and abdominal esophageal defects in the rat.

Porcine small intestinal submucosa (SIS) is a cell-free collagen matrix that has demonstrated its ability as scaffold material for constructive remodeling of damaged or missing tissue. The purpose of this study was to evaluate the morphology and function of esophagoplasty in rat using a porcine SIS scaffold for the repair of a semi-circumferential defect in the cervical or in the abdominal esophagus. Sixty-seven rats underwent surgical excision of the anterior wall either of the cervical or of the abdominal esophagus and subsequent repair of the defect with an SIS patch graft. Outcomes of weight gain, signs of dysphagia, hematological and serum chemistry parameters, and barium swallow studies were used to assess the progress of healing and function over a 150-day time period. The grafts were studied for gross changes and histology at predetermined time points. Ninety-four percent of the SIS-treated rats survived, showing no significant differences in survival rate between groups. The grafted animals did well, without signs of dysphagia, and gaining weight. Barium swallow studies showed no evidence of fistula, significant stenosis, or diverticula. No hematological or serum biochemistry abnormalities were found. By 150 days, the SIS graft was replaced with esophageal-derived tissues. Specimens were completely lined by keratinized stratified squamous epithelium and showed complete regeneration of muscle fibers and scarce immunoreactivity for nerve. In the rat model, a patch graft technique using porcine SIS appears to induce esophageal regrowth either in cervical and abdominal esophagus. The repair mechanism occurred through a regenerative healing process.     

Brachial endothelial function in subjects with familial combined hyperlipidemia and its relationships to carotid artery intima-media thickness.

AIM: The aim of this study was to quantify the flow-mediated dilatation (FMD) of brachial artery in asymptomatic members of families with familial combined hyperlipidemia (FCH) and to determine the relation between FMD and risk factors accompanying FCH. We also investigated the association between FMD and the intima-media thickness (IMT) of the common carotid artery. METHODS: Eighty-two members of 29 FCH families were divided into two groups: probands and hyperlipidemic first-degree relatives (HL) (n=47) and normolipidemic first-degree relatives (NL) (n=35). The control (C) groups, C-HL (n=20) and C-NL (n=20), consisted of sex- and age-matched healthy individuals. FMD was assessed in the brachial artery by measuring the change in brachial artery diameter in response to reactive hyperemia. RESULTS: Both hyperlipidemic subjects and their NL had significantly lower FMD (3.4+/-3% vs 6.3+/-2.8%, P<0.001, 5.2+/-2.3% vs 7.8+/-2.8%, P<0.01, respectively) compared to controls. In multivariate backward stepwise regression analysis, FMD in members of FCH families was independently associated with sex (P<0.001), age (P<0.01), C-peptide (P<0.05) and borderline with glycemia (P=0.052). FMD correlated inversely with IMT in all subjects of FCH families and in hyperlipidemic members. In multivariate backward stepwise regression analysis this relation remained independent (P<0.001, P<0.01, respectively). CONCLUSIONS: Members of FCH families showed impaired FMD, which was independently associated with markers of insulin resistance. FMD and IMT were independently associated in hyperlipidemic, but not in normolipidemic members of FCH families.     

Modulation of arterial stiffness with intensive competitive training.

BACKGROUND: Aerobic exercise training has been associated with beneficial effects on the cardiovascular system, improving arterial compliance, possibly related to a positive impact on the endothelium. The effects of competitive aerobic exercise are not so well documented. This prompted us to evaluate the possible modulation of arterial properties in a group of athletes and their response to the aging process. METHODS: 423 healthy males were enrolled in a cross-sectional study, 212 of whom were competitive athletes and 211 were controls. All underwent carotid-femoral pulse wave velocity (PWV) evaluation, and casual blood pressure and other relevant anthropometric data were evaluated. RESULTS: To control the effects of age, each group was divided into two subgroups with an age cut-point of 20 years. PWV was 6.3 +/- 0.9 m/s (athletes) vs. 7.0 +/- 1.0 m/s (controls) for ages <20 years, and 7.6 +/- 1.2 m/s (athletes) vs. 8.1 +/- 0.9 m/s (controls) for ages >20 years, with statistically significant differences in both comparisons. A linear regression model with logarithmic tendency analysis with age as the independent determinant of PWV revealed a different progression of age-related deterioration of aortic compliance between the two groups (athletes and controls). CONCLUSIONS: Our data documented better compliance indices in competition athletes compared with controls, which may reflect optimization of endothelial function. This improvement was age-dependent, being less pronounced as the athletes grow older, which could be due partially to sustained stretching effects on the arterial walls in long-term competitors.     

Estimation of salt intake by urinary sodium excretion in a Portuguese adult population and its relationship to arterial stiffness.

BACKGROUND: Portugal has one of the highest mortality rates from stroke, a high prevalence of hypertension and probably a high salt intake level. AIM: To evaluate Portuguese salt intake levels and their relationship to blood pressure and arterial stiffness in a sample of four different adult populations living in northern Portugal. METHODS: A cross-sectional study evaluating 24-hour urinary excretion of sodium (24 h UNa+), potassium and creatinine, blood pressure (BP), and pulse wave velocity (PWV) as an index of aortic stiffness in adult populations of sustained hypertensives (HT), relatives of patients with previous stroke (Fam), university students (US) and factory workers (FW), in the context of their usual dietary habits. RESULTS: We evaluated a total of 426 subjects, mean age 50 +/- 22 years, 56% female, BMI 27.9+/-5.1, BP 159/92 mmHg, PWV 10.4+/-2.2 m/s, who showed mean 24h UNa+ of 202 +/- 64 mmol/d, corresponding to a daily salt intake of 12.3 g (ranging from 5.2 to 24.8). The four groups were: HT: n = 245, 49 +/- 18 years, 92% of those selected, 69% treated, BP 163/94 mmHg, PWV 11.9 m/s, 24 h UNa+ 212 mmol/d, i.e. 12.4 g/d of salt); Fam: n = 38, 64 +/- 20 years, 57 % of those selected, BP 144/88 mmHg, PWV 10.5 m/s, 24 h UNa+ 194 mmol/d, i.e. 11.1 g/d of salt; US: n = 82, 22 +/- 3 years, 57% of those selected, BP 124/77 mmHg, PWV 8.7 m/s, 24h UNa+ 199 mmol/d, i.e. 11.3 g/d of salt; FW: n = 61, 39 9 years, 47% of those selected, BP 129/79 mmHg, PWV 9.5 m/s, 24 h UNa+ 221 mmol/d, i.e. 12.9 g/d of salt. The ratio of urinary sodium/potassium excretion (1.9 (0.4) was significantly higher in HT than the other three groups. In the 426 subjects, 24h UNa+ correlated significantly (p < 0.01) with systolic BP (r = 0.209) and with PWV (r=0.256) after adjustment for age and BP. Multivariate analysis showed that BP, age and 24h UNa+ correlated independently with PWV taken as a dependent variable. CONCLUSIONS: Four different Portuguese populations showed similarly high mean daily salt intake levels, almost double those recommended by the WHO. Overall, high urinary sodium excretion correlated consistently with high BP levels and appeared to be an independent determining factor of arterial stiffness. These findings suggest that Portugal in general has a high salt intake diet, and urgent measures are required to restrict salt consumption in order to prevent and treat hypertensive disease and to reduce overall cardiovascular risk and events.     

The cognit: a network model of cortical representation.

The prevalent concept in modular models is that there are discrete cortical domains dedicated more or less exclusively to such cognitive functions as visual discrimination, language, spatial attention, face recognition, motor programming, memory retrieval, and working memory. Most of these models have failed or languished for lack of conclusive evidence. In their stead, network models are emerging as more suitable and productive alternatives. Network models are predicated on the basic tenet that cognitive representations consist of widely distributed networks of cortical neurons. Cognitive functions, namely perception, attention, memory, language, and intelligence, consist of neural transactions within and between these networks. The present model postulates that memory and knowledge are represented by distributed, interactive, and overlapping networks of neurons in association cortex. Such networks, named cognits, constitute the basic units of memory or knowledge. The association cortex of posterior-post-rolandic-regions contains perceptual cognits: cognitive networks made of neurons associated by information acquired through the senses. Conversely, frontal association cortex contains executive cognits, made of neurons associated by information related to action. In both posterior and frontal cortex, cognits are hierarchically organized. At the bottom of that organization-that is, in parasensory and premotor cortex-cognits are small and relatively simple, representing simple percepts or motor acts. At the top of the organization-in temporo-parietal and prefrontal cortex-cognits are wider and represent complex and abstract information of perceptual or executive character. Posterior and frontal networks are associated by long reciprocal cortico-cortical connections. These connections support the dynamics of the perception-action cycle in sequential behavior, speech, and reasoning.     

Acute resynchronization with inhaled iloprost in a pregnant woman with idiopathic pulmonary artery hypertension.

We describe the case of a pregnant woman with idiopathic pulmonary arterial hypertension, a responder in right heart catheterization, followed since the first trimester in outpatient consultations, admitted to hospital at 23 weeks gestation. She was treated with inhaled iloprost until delivery (at 34 weeks gestation) and continuous infusion of iloprost throughout the perioperative period and following days. This line of therapy has proved efficacious in previous cases. The authors present echocardiographic images that document acute changes in ventricular synchrony during inhalation of iloprost.     

Sequential study on the treatment of moderate-to-severe chronic plaque psoriasis with mycophenolate mofetil and cyclosporin

BACKGROUND: There are numerous studies that individually evaluate the efficacy/effectiveness and toxicity of drugs in the systemic treatment of psoriasis. On the contrary, we can hardly find studies that compare each other. OBJECTIVE: To evaluate and compare the effectiveness and toxicity of mycophenolate mofetil and cyclosporin in chronic plaque psoriasis through a prospective, sequential, cross-over, non-randomized, two-phase, open-label study. PATIENTS/METHODS: Eight patients (five women and three men; mean age 57, range 35-78) with moderate-to-severe chronic plaque psoriasis were included in the study. They were treated with oral mycophenolate mofetil (30 mg/kg/day) over a period of 16 weeks. Following a variable washout period and after a new outbreak of the disease, oral cyclosporin was introduced at a dose of 4 mg/kg/day. During both treatment regimens, follow-up visits were performed at 3, 8 and 16 weeks. RESULTS: In both groups, the PASI started to decrease once treatment was begun. Cyclosporin was faster and statistically a lot more effective than mycophenolate mofetil, reaching a higher number of complete remissions and better percentages of PASI improvement from baseline (45.7%, 60.2% and 60.5% at 3, 8 and 16 weeks respectively for mycophenolate mofetil, and 89.7%, 95.3% and 95.3% respectively at the same intervals for cyclosporin). Cyclosporin was also more predictable in its action as the percentage of improvement along the follow-up visits had a much wider range for mycophenolate mofetil. Overall, the tolerability of both drugs was good. None of the patients had to discontinue treatment because of an adverse event. Two patients treated with cyclosporin showed increased plasma levels of creatinine. CONCLUSIONS: Cyclosporin is more effective, fast, and predictable in its effect than mycophenolate mofetil to control moderate-to-severe chronic plaque psoriasis. Both drugs are well tolerated in short courses of treatment.     

Induction of intercellular adhesion molecule-1 but not of lymphocyte function-associated antigen-3 in thyroid follicular cells.

We investigated the expression of intercellular adhesion molecule-1 (ICAM-1) and lymphocyte function-associated antigen-3 (LFA-3) by thyrocytes and their regulation by cytokines. Immunofluorescence studies on cryostat sections and on freshly dispersed cell preparations showed that ICAM-1 and LFA-3 are barely detectable in non-autoimmune thyrocytes. However, thyrocytes acquired ICAM-1 expression in culture. IFN-gamma, IL-1 beta and TNF-alpha produced a clear enhancement of ICAM-1 expression. When tested in combination, IL-1 beta and TNF-alpha were additive to the IFN-gamma effect. LFA-3 expression was not modulated by these cytokines. In the HT93 thyroid cell line generated by transfection with SV40, ICAM-1 and LFA-3 were both constitutively expressed at high levels. Cytokines modulated ICAM-1 expression similarly, but to a greater extent than in normal thyrocytes. LFA-3 remained unmodified. These results support the notion that normal thyrocytes are immunologically silent cells. The capability of cytokines to induce ICAM-1 together with HLA class I and class II-expression on thyrocytes suggests that under their influence, these cells may express all the surface molecules required for antigen presentation and/or for being recognized as target cells in the context of thyroid autoimmune disease.     

Bradycardia related to hypoglycaemia.

Alterations in blood glucose levels are known to be involved in electrocardiogram changes. Various types of arrhythmias have been reported. We present here the case of an 81-year-old woman presenting with transient atrial fibrillation while being treated for hypoglycaemia with dextrose infusion, and finally developing a sinus rhythm. The presence of alterations in glucose blood levels should always be considered as a potential cause of transient atrial fibrillation.