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Biomedical subjects

M Porta

Publications and source records attributed to M Porta.

At least 199 records · Page 11Linked to original sources

Homovanillic acid and 5-hydroxyindole-acetic acid in the csf of patients after a severe head injury. I. Lumbar csf concentration in chronic brain post-traumatic syndromes.

Lumbar CSF concentrations of homovanillic acid (HVA) and 5-hydroxyindole-acetic acid (5HIAA) have been determined in ten patients suffering from chronic brain post-traumatic syndromes, at various length of time after the brain trauma. Lower concentrations of HVA (mean 21 +/- 14 mug/ml) compared to controls (mean 46 +/- 10 mug/ml) was observed in 7 cases; 5HIAA levels were within normal values. The 5HIAA/HVA ratio (1.59 +/- 0.66) was significantly higher (p less than 0.001) than the one recorded in controls (0.66 +/- 0.10). Monitoring of lumbar HVA and 5HIAA over time, before, during and after L-dopa treatment, revealed interesting correlations between modification of clinical picture and the levels of monoamines acid metabolites. The data indicate a profound alteration of brain monoamines in chronic syndromes following a severe head injury and suggest that measurements of lumbar HVA and 5HIAA in these patients may be of euristic and diagnostic value.

Adolescent↗

Homovanillic acid and 5-hydroxyindole-acetic acid in the csf of patients after a severe head injury. II. Ventricular csf concentrations in acute brain post-traumatic syndromes.

Ventricular concentrations of homovanillic acid (HVA) and 5-hydroxyindole-acetic acid (5HIAA) were measured in 7 patients a few days after a severe traumatic brain injury. Both acid metabolites were elevated in respect to control patients values, however, the rise was more consistent for 5HIAA (258 +/- 86 ng/ml) with a 5HIAA/HVA ratio of 0.85 +/- 0.35. The data support previous hypothesis on the profound involvement of serotoninergic structures in the early stages of acute traumatic brain syndromes and on the role of 5HT in maintaining edema and vasospasm.

Adolescent↗

Thiamine and benfotiamine prevent increased apoptosis in endothelial cells and pericytes cultured in high glucose.

BACKGROUND: High glucose induces pathological alterations in small and large vessels, possibly through increased formation of AGE, activation of aldose reductase and protein kinase C, and increased flux through the hexosamine pathway. We showed previously that thiamine and benfotiamine correct delayed replication and increase lactate production in endothelial cells subjected to high glucose. We now aim at verifying the effects of thiamine and benfotiamine on cell cycle, apoptosis, and expression of adhesion molecules in endothelial cells and pericytes, under high ambient glucose. METHODS: Human umbilical vein endothelial cells and bovine retinal pericytes were cultured in normal (5.6 mmol/L) or high (28 mmol/L) glucose, with or without thiamine or benfotiamine, 50 or 100 micro mol/L. Apoptosis was determined by two separate ELISA methods, measuring DNA fragmentation and caspase-3 activity, respectively. Cell cycle and integrin subunits alpha3, alpha5, and beta1 concentration were measured by flow cytometry. RESULTS: Apoptosis was increased in high glucose after 3 days of culture, both in endothelium and pericytes. Thiamine and benfotiamine reversed such effects. Neither cell cycle traversal nor integrin concentrations were modified in these experimental conditions. CONCLUSIONS: Thiamine and benfotiamine correct increased apoptosis due to high glucose in cultured vascular cells. Further elucidations of the mechanisms through which they work could help set the basis for clinical use of this vitamin in the prevention and/or treatment of diabetic microangiopathy.

Animals↗

Serum concentrations of organochlorine compounds and K-ras mutations in exocrine pancreatic cancer. PANKRAS II Study Group.

BACKGROUND: Organochlorine compounds such as 1,1,1-trichloro-2,2-bis(p-chlorophenyl)-ethane (p,p'-DDT), 1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene (p,p'-DDE), and some polychlorinated biphenyls (PCBs) are carcinogenic to animals and possibly also to human beings. Occupational exposure to DDT may increase the risk of pancreas cancer. The high frequency of K-ras mutations in pancreatic cancer remains unexplained. We analysed the relation between serum concentrations of selected organochlorine compounds and mutations in codon 12 of the K-ras gene in patients with exocrine pancreatic cancer. METHODS: Cases were prospectively identified in five hospitals. Mutations in K-ras were analysed by PCR and artificial restriction fragment length polymorphism. Cases of pancreatic cancer with wild-type K-ras (n=17) were frequency matched for age and sex to cases of pancreatic cancer with a K-ras mutation (n=34, case-case study). These 51 cases were further compared with 26 hospital controls (case-control comparison). Serum organochlorine concentrations were measured by high-resolution gas chromatography with electron-capture detection and negative ion chemical ionisation mass spectrometry. FINDINGS: Serum concentrations of p,p'-DDT were significantly higher in pancreatic cancer cases with a K-ras mutation than in cases without a mutation (odds ratio for upper tertile 8.7 [95% CI 1.6-48.5], p for trend=0.005). For p,p'-DDE the corresponding figures were 5.3 (1.1-25.2, p for trend=0.031). These estimates held after adjusting for total lipids, other covariates, and total PCBs. A specific association was observed between a glycine to valine substitution at codon 12 and both p,p'-DDT and p,p'-DDE concentrations (odds ratio 15.9, p=0.044 and odds ratio 24.1, p=0.028; respectively). A similar pattern was shown for the major di-ortho-chlorinated PCBs (congeners 138, 153, and 180), even after adjustment for p,p'-DDE, but without a specific association with spectrum. Concentrations of p,p'-DDT and p,p'-DDE were similar among wild-type cases and controls, but significantly higher for K-ras mutated cases than for controls (p<0.01). INTERPRETATION: Organochlorine compounds such as p,p'-DDT, p,p'-DDE, and some PCBs could play a part in the pathogenesis of exocrine pancreatic cancer through modulation of K-ras activation. The results require replication, but they suggest new roles for organochlorines in the development of several cancers in human beings.

Aged↗

[Concentrations of persistent toxic compounds in the Spanish population: a puzzle without pieces and the protection of public health].

The contamination by persistent toxic compounds (PTCs) of the general population is a fact of relevance from a public health perspective. It is also relevant to health care professionals, as well as for environmental, food, industrial and economic policies. Though in Spain information on food contamination by PTCs shows large time and geographic gaps, the scarcity of data is even more severe on the concentrations that PTCs have in people: a representative study of a general healthy population living in a wide geographic area has never been conducted in the country. However, the available studies indicate that around 80-100% of the population has detectable concentrations of DDE, PCBs, hexachlorbenzene or lindane. Studies on the effects that PTCs have upon humans are extremely infrequent in Spain. Yet, the international literature suggests that some PTCs may induce significant biological and clinical effects at doses below those traditionally deemed "safe". The mechanism of action of PTCs are not restricted to endocrine disruption. Assessing the clinical and social relevance of the more subtle and long-term effects of PTCs presents interesting challenges and opportunities. Spain and other European countries lack population indicators on the impact that environmental processes have on human health. Several government levels have a role to fulfill in the monitoring of biological levels of PTCs among persons in order to assess the risks of adverse health effects. Along with over a hundred other countries. Spain will soon try to implement the Stockholm treaty on persistent organic pollutants (POPs). This constitutes a new opportunity to develop more efficient policies to control PTC residues in food, humans and the environment. As part of the treaty implementation it is necessary to launch a Report on factors that influence body concentrations of PTCs in the Spain general population.

Animals↗

[Agreement between information supplied by the patient and a family member on medical history, consumption of tobacco, alcohol and coffee and diet in cancer of the exocrine pancreas and extrahepatic biliary tract].

OBJECTIVE: No study on mutations in the K-ras oncogene and cancer of the exocrine pancreas or cancer of the biliary system has analyzed the reliability of clinical and epidemiological information. METHODS: Agreement between patient and surrogate on factors potentially related to both tumours was evaluated within a multicentre prospective study. Interviews were personally administered to both patient and surrogate (N = 110 pairs). Agreement was examined via the simple kappa index (k), the weighted kappa index (kw), the percentage of simple agreement, and the percentages of positive and negative agreement. RESULTS: Agreement for medical history was excellent (k between 0.89 and 0.76), as it was for tobacco consumption (k = 0.98). Agreement was moderate for coffee consumption (k = 0.68), frequencies of food groups (kw from 0.66 to 0.38), and consumption of alcoholic drinks (k from 0.66 to 0.32). Surrogates indicated a higher consumption of alcohol than patients. CONCLUSION: Surrogates can be an alternative source of information when patients cannot be interviewed, but information on alcohol consumption should be treated with caution.

Adult↗

Protocols for screening and treatment of diabetic retinopathy in Europe.

Diabetes eye complications, and particularly diabetic retinopathy, are the major cause of blindness in the working age groups of industrialised countries. Laser photocoagulation has been proven to reduce blindness due to retinopathy by at least 60% but even more patients would benefit if treatment were delivered at an early enough stage. High risk retinopathy, though, does not cause visual symptoms and when the latter occur it is often too late to reverse them. Hence, a screening programme for diabetic retinopathy should aim at detecting patients at risk when they can still be effectively treated. This can be obtained by regularly checking the patients' eyes. Its target, as defined by the joint World Health Organisation/International Diabetes Federation Saint Vincent Declaration Working Group, is to reduce diabetes-related blindness by one third or more in the next 5 years. The number of persons to be screened is high, 30,000/million total population/year, but available data indicate that this is feasible and that the initial investments in professional and material resources are more than justified by the reduction of preventable blindness and of the financial burdens that go with it. Indeed, prevention of the major cause of blindness in the working age should rate the same priority as other widely deployed programmes, such as those to screen for cancer, neonatal hypothyroidism and phenylketonuria. The concerted action of government health departments, patients' and professional associations will be vital for the successful implementation of this programme. The texts of this document (a protocol for the screening of diabetic retinopathy and cataract), Appendix 1 (data collection card) and Appendix 2 (informative leaflet for the patients) were approved by 57 specialists, representing 30 diabetic and ophthalmic societies from 21 European countries, and endorsed for translation into all European languages and distribution at the appropriate levels.

Cataract Extraction↗

A study of the effects of angiotensins 1, 2, 3 and bradykinin on the replication of bovine retinal capillary endothelial cells and pericytes.

The renin-angiotensin system of the human eye may play a role in the regulation of retinal blood flow and the development of new vessels. We have investigated whether angiotensins 1, 2 and 3 or bradykinin, in concentrations ranging between 1 x 10(-12) and 1 x 10(-6), have any mitogenic activity on cultured bovine retinal endothelial cells (BREC) and pericytes (BRP). Cell replication was assessed by 3H-thymidine incorporation and, in the case of BREC and AT-2, also by cell counts. AT-2 was also tested on bovine aortic EC (BAEC). None of the substances elicited any response on BREC, BRP or BAEC. Whether angiotensin(s) induce angiogenesis in retinal vessels in vivo remains to be established but this does not appear to occur through direct stimulation of cell replication.

Angiotensins↗

Diabetic retinopathy and metabolic control.

Retinopathy is probably the first long-term complication of diabetes mellitus to become clinically evident, possibly because the retina is the only microvascular bed that can be observed directly and repeatedly. This makes it a good model for studying the pathogenesis and natural history of diabetic microangiopathy. Most of the proposals to account for its pathogenesis invoke mechanisms that depend directly on the circulating and tissue levels of glucose: protein glycosylation, activation of the "polyol pathway", abnormalities of vascular endothelium, altered capillary blood flow. Several population studies and clinical trials suggest that the degree of metabolic control maintained over the years influences the rates of appearance and progression of retinopathy. However, on an individual basis, factors independent of control may intervene, making some patients more or less prone to this complication. Animal models also suggest that the progression of retinopathy may become irreversible from its very early stages. From a clinical point of view, it is difficult to establish a satisfactory definition of "good" control and approaching it may increase the risk of dangerous hypoglycemia and weight gain. Diabetes and eye specialists are thus left to strive for the best possible, sensible, metabolic control but must also rely on early diagnosis and treatment for the sight-threatening complications of diabetes.

Anecdotes as Topic↗

Diabetic retinopathy: are we really doing all we can for our patients?

Although it is now possible to significantly reduce the incidence of blindness secondary to diabetes mellitus, large numbers of diabetic patients still experience visual loss due to retinal complications of the disease. This implies that protocols for the diagnosis and treatment of diabetic retinopathy used in the various multicenter trials have not yet been transferred into routine clinical practice. In countries where ocular complications of diabetes have been managed on the basis of well-codified protocols for several years, the incidence of visual loss among diabetic patients has been significantly reduced. It is absolutely essential to introduce screening and treatment protocols for diabetic retinopathy promptly everywhere. Their application is within the reach of every ophthalmologist. Patients must be informed that it is important to have regular full ophthalmological examinations, before any symptoms occur; the guidelines for screening and management of retinopathy must be known and accepted by the medical community. Spreading this information among primary care physicians, ophthalmologists and diabetologists is a fundamental step in improving the health care of the diabetic patient.

Clinical Protocols↗