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Biomedical subjects

S Boschi

Publications and source records attributed to S Boschi.

At least 37 records · Page 2Linked to original sources

Opioid peptide modulation of circulatory and endocrine response to mental stress in humans.

Healthy subjects were classified according to their percent increase in systolic blood pressure (SBP) after mental arithmetic test (MAT) as low (delta SBP 9.3-15.1%, n = 15) and high (delta SBP 35.1-45.4%, n = 15) responders. During MAT, low responders showed significantly (p < 0.01) increased plasma levels of beta-endorphin, cortisol, catecholamines, and atrial natriuretic factor (ANF) and decreased levels of endothelin-1, whereas high responders showed increased (p < 0.01) levels of Metenkephalin, dynorphin B, and catecholamines. Pretreatment with naloxone hydrochloride enhanced (p < 0.01) SBP, heart rate, noradrenaline, cortisol, and endothelin-1 levels, and reduced (p < 0.01) ANF in low responders in response to MAT, whereas it decreased (p < 0.01) hemodynamic parameters, noradrenaline, and endothelin-1 in high responders. The individual differences in hemodynamic and endocrine responses to MAT may depend on a different activation of the endogenous opioid system.

Adult↗

Protective effects of delapril, indapamide and their combination chronically administered to stroke-prone spontaneously hypertensive rats fed a high-sodium diet.

1. Stroke-prone spontaneously hypertensive rats (SHRsp) have been used widely to test agents putatively capable of vascular protection. These animals present an accelerated time course of hypertension and a reduced life-span. When fed a high-sodium diet from the eighth week of life, a further acceleration in blood pressure increase is obtained, and rats start to die after 5 weeks of diet as a consequence of cerebral haemorrhage. In this model, angiotensin-converting enzyme (ACE) inhibitors were repeatedly proved to prevent vascular lesions and death. Notably, this effect was independent of any hypotensive effect. On the contrary, diuretics were shown not to be equally effective. A combination of ACE inhibitors and diuretics, although known to have synergistic effects in the therapy of hypertension, has never previously been tested. 2. Our aim was to study the effects of long-term treatment with the ACE inhibitor delapril (12 mg day-1 kg-1), the thiazide-like diuretic indapamide (1 mg day-1 kg-1), and their combination (12 and 1 mg day-1 kg-1 respectively), on the survival of SHRsp rats fed a high-sodium diet from the eighth week of life onwards. The effects of the treatments on blood pressure, body weight, food and fluid intake, diuresis, proteinuria and the appearance of lesion signs and death were assessed weekly. When control rats reached 50% mortality, they were killed, together with some drug-treated rats, to compare lesions in brain and kidney. The other drug-treated rats continued treatments until 50% mortality was reached in two treatment groups. 3. All drug treatments were able to delay death significantly when compared with control rats, which reached 50% mortality after 6 weeks of salt loading. This event was preceded by a highly significant increase in proteinuria, diuresis and fluid intake that took place 3 weeks after the increase in blood pressure over the initial range. In delapril- or indapamide-treated SHRsp these changes were never seen, even when animals started to die. In the combination-treated group, a significant increase (P < 0.01) in fluid intake and diuresis, but not proteinuria, was observed from the third week of treatment onwards. 4. Treatment with delapril or indapamide did not block the progressive increase in blood pressure as observed in control animals. However, the increase in blood pressure was markedly retarded with respect to control rats. At variance with this, in combination-treated animals blood pressure levels were maintained until the end of the experiment within the 99% confidence interval initially observed in control animals. 5. Infarctual and haemorrhagic cerebral lesions were observed in 38% of control rats; no lesions were noted in brains of age-matched rats receiving a drug treatment. Kidneys from control animals presented major degenerative lesions of glomeruli and arteries, characterized by fibrinoid necrosis. This condition was absent in drug-treated animals, which presented minor signs of ischaemic lesion. Heart hypertrophy, when heart weight was expressed as a percentage of body weight, was similar in saline-, delapril- or indapamide-treated rats. At variance with this, in combination-treated animals the heart weight to body weight ratio was significantly (P < 0.01) lower than in the other groups. 6. In conclusion, the diuretic indapamide showed similar protective effects as the ACE inhibitor delapril on acute vascular lesions and survival of SHRsp. Moreover, their combination synergized in preventing heart hypertrophy consequent to longterm hypertension. This results is probably related to the enhanced diuresis and the better control of blood pressure levels selectively found in combination-treated animals.

Analysis of Variance↗

Retrograde colonic spread of a new mesalazine rectal enema in patients with distal ulcerative colitis.

BACKGROUND: Rectal treatment with mesalazine enemas is the first-line therapy for distal ulcerative colitis. In order to improve the benefits of rectal therapy, a new 60 mL 5-ASA rectal gel enema preparation has been developed using a device which excludes direct contact of the inert propellant gas with the active drug. The purpose of the present study was to assess by scintigraphy the colonic distribution of this new mesalazine rectal gel enema. METHODS: Twelve patients with active ulcerative colitis were administered 4 g of the mesalazine rectal enema labelled with 100 MBq technetium sulphur colloid (99mTc-SC). Anterior scans of the abdomen were acquired at intervals for 4 h. Scans were analysed to evaluate the extent of retrograde flow and homogeneity of distribution of the radiolabelled enema in the rectum, sigmoid, descending and transverse colon. In addition, plasma levels of 5-ASA and Ac-5-ASA were measured for 6 h. RESULTS: All patients retained the entire rectal gel throughout the course of the study without reporting adverse events. In 11 out of 12 patients (92%) the gel had spread homogeneously beyond the sigmoid colon and had reached the upper limit of disease in all cases. The maximum spread (splenic flexure) was observed in 6 out of 12 patients (50%) within the first 2 h. The systemic absorption of mesalazine and its metabolite Ac-5-ASA was low. CONCLUSIONS: The new mesalazine enema represents an adequate alternative and a further technological improvement in the topical treatment of distal ulcerative colitis.

Adult↗

Developmental pattern of fetal growth hormone, insulin-like growth factor I, growth hormone binding protein and insulin-like growth factor binding protein-3.

AIMS: To evaluate the developmental pattern of fetal growth hormone (GH), insulin-like growth factor I (IGF-I), GH binding protein (GHBP) and IGF binding protein-3 (IGF-3); to determine the implications for fetal growth. METHODS: Serum GH, IGF-I, GHBP and IGFBP-3 were measured in 53 fetuses, 41 aged 20-26 weeks (group A) and 12 aged 31-38 weeks (group B). Fetal blood samples were obtained by direct puncture of the umbilical vein in utero. Fetal blood samples were taken to rule out beta thalassaemia, chromosome alterations, mother to fetus transmissible infections, and for maternal rhesus factor. GHBP was determined by gel filtration chromatography of serum incubated overnight with 125I-GH. GH, IGF-I and IGFBP-3 were determined by radioimmunoassay. RESULTS: Fetal serum GH concentrations in group A (median 29 micrograms/l, range 11-92) were significantly higher (P < 0.01) than those of group B (median 16.7 micrograms/l, range 4.5-29). IGF-I in group A (median 20 micrograms/l, range 4.1-53.3) was significantly lower (P < 0.01) than in group B (median 75.2 micrograms/l, range 27.8-122.3). Similarly, IGFBP-3 concentrations in group A (median 950 micrograms/l, range 580-1260) were significantly lower than those of group B (median 1920 micrograms/l, range 1070-1770). There was no significant difference between GHBP values in group A (median 8.6%, range 6.6-12.6) and group B (median 8.3%, range 6-14.3). Gestational age correlated positively with IGF-I concentrations (P < 0.0001) and IGFBP-3 (P < 0.0001) and negatively with GH (P < 0.0001). GHBP values did not correlate with gestational age. Multiple regression analysis showed a negative correlation between GH:IGF-I ratio and fetal growth indices CONCLUSIONS: The simultaneous evaluation of fetal GH, IGF-I, IGFBP-3 and GHBP suggests that the GH-IGF-I axis might already be functional in utero. The progressive improvement in the efficiency of this axis in the last part of gestation does not seem to be due to an increase in GH receptors.

Biomarkers↗

Pressor effects of endogenous opioid system during acute episodes of blood pressure increases in hypertensive patients.

To investigate the involvement of endogenous opioids in acute increases in blood pressure and their functional relationship with atrial natriuretic factor and endothelin-1, we assessed plasma levels of beta-endorphin, met-enkephalin, dynorphin B, catecholamines, atrial natriuretic factor, and endothelin-1 before and after administration of the opioid antagonist naloxone hydrochloride (8 mg i.v.) in 28 hypertensive patients with a stress-induced acute increase in blood pressure. Ten patients with established mild or moderate essential hypertension and 10 normotensive subjects served as control groups. Opioids, atrial natriuretic factor, and endothelin-I were radioimmunoassayed after chromatographic preextraction; catecholamines were determined by high-performance liquid chromatography with electrochemical detection. Patients with an acute increase in blood pressure (systolic, 203.2 +/- 2.2 mm Hg; diastolic, 108.4 +/- 1.3) had plasma opioid, catecholamine, and atrial natriuretic factor levels significantly (P < .01) higher than hypertensive control patients (systolic pressure, 176.4 +/- 1.0 mm Hg; diastolic, 100.0 +/- 1.4), who had a hormonal pattern similar to that of normotensive subjects (systolic pressure, 123.2 +/- 1.5 mm Hg; diastolic, 75.0 +/- 2.0). Endothelin-1 did not differ in any group. In patients with an acute increase in blood pressure, naloxone significantly (P < .01) reduced blood pressure, heart rate, opioids, catecholamines, and atrial natriuretic factor 10 minutes after administration. Naloxone effects on blood pressure, heart rate, opioids, and catecholamines wore off within 20 minutes. In control groups, naloxone failed to modify any of the considered parameters. Our findings suggest that pressor effects of opioid peptides mediated by the autonomic nervous system during stress-induced acute episodes of blood pressure increase in hypertensive patients.

Atrial Natriuretic Factor↗

Effect of an enteric-coated fish-oil preparation on relapses in Crohn's disease.

BACKGROUND: Patients with Crohn's disease may have periods of remission, interrupted by relapses. Because fish oil has antiinflammatory actions, it could reduce the frequency of relapses, but it is often poorly tolerated because of its unpleasant taste and gastrointestinal side effects. METHODS: We performed a one-year, double-blind, placebo-controlled study to investigate the effects of a new fish-oil preparation in the maintenance of remission in 78 patients with Crohn's disease who had a high risk of relapse. The patients received either nine fish-oil capsules containing a total of 2.7 g of n-3 fatty acids or nine placebo capsules daily. A special coating protected the capsules against gastric acidity for at least 30 minutes. RESULTS: Among the 39 patients in the fish-oil group, 11 (28 percent) had relapses, 4 dropped out because of diarrhea, and 1 withdrew for other reasons. In contrast, among the 39 patients in the placebo group, 27 (69 percent) had relapses, 1 dropped out because of diarrhea, and 1 withdrew for other reasons (difference in relapse rate, 41 percentage points; 95 percent confidence interval, 21 to 61; P < 0.001). After one year, 23 patients (59 percent) in the fish-oil group remained in remission, as compared with 10 (26 percent) in the placebo group (P = 0.003). Logistic-regression analysis indicated that only fish oil and not sex, age, previous surgery, duration of disease, or smoking status affected the likelihood of relapse (odds ratio for the placebo group as compared with the fish-oil group, 4.2; 95 percent confidence interval, 1.6 to 10.7). CONCLUSIONS: In patients with Crohn's disease in remission, a novel enteric-coated fish-oil preparation is effective in reducing the rate of relapse.

Adult↗

Intrapatient comparison of atrial and ventricular sensing, pacing threshold, and impedance: benefits with steroid-eluting leads.

We compared the atrial and ventricular bio-electrical effects relating to pacing threshold, pacing impedance, and pacing energy in each of 58 patients to determine the importance of pacing impedance in safe low energy stimulations. The study was conducted during 4 years of follow-up. Of the 58 patients in our study, 31 were stimulated in both chambers with steroid-eluting leads (Capsure 4503 and 4003) and 27 with platinum electrode catheters (Target Tip 4511 and 4011). The two groups were homogeneous in sex, age, cardiopathy, and reason for implant. At 6 months, the mean impedance values for the Target Tip were: 358 +/- 72 omega for the atrium and 443 +/- 72 omega for the ventricle (P < 0.00002); after 1 year, atrium = 386 +/- 77 omega, ventricle = 439 +/- 42 omega (P < 0.04); at 2 years, atrium = 409 +/- 86 omega, ventricle = 510 +/- 94 omega (P < 0.0001); at 3 years, atrium = 428 +/- 81 omega, ventricle = 494 +/- 67 omega (P < 0.02); and at 4 years, atrium = 424 +/- 71 omega and ventricle = 501 +/- 69 omega (P < 0.003). The mean impedance value (for the Capsure) was: atrium = 351 +/- 43 omega, ventricle = 431 +/- 81 omega at 6 months (P < 0.03); at 1 year, atrium = 359 +/- 38 omega, ventricle = 446 +/- 83 omega (P < 0.01); at 2 years, atrium = 304 +/- 124 omega, ventricle = 459 +/- 108 omega (P < 0.0003); at 3 years, atrium = 359 +/- 108 omega, ventricle = 461 +/- 89 omega (P < 0.02); and at 4 years, atrium = 419 +/- 133 omega and ventricle = 515 +/- 75 omega (P < 0.01). In view of the chronic threshold, low energy stimulation was used at follow-up. The mean low energy stimulation values programmed for Target Tip were: atrium = 2.5 V/0.35 ms, ventricle = 2.5 V/0.30 ms; for Capsure, atrium = 2.5 V/0.25 ms, ventricle = 2.5 V/0.25 ms. The mean stimulation energy value was 31% higher in the atrium than in the ventricle with Capsure leads, and 39% higher with Target Tip. Pacing impedance was lower in the atrium than in the ventricle with both leads. Energy consumption in the atrium is significantly greater than in the ventricle with both leads, particularly with Target Tip.

Aged↗

Low dose of ACE-inhibitor enhances sodium excretion in volume expanded patients with borderline hypertension.

The purpose of the present study was to separately investigate the effects of two different dosages of captopril on pressor, vascular and humoral response to acute extracellular volume expansion in patients with borderline hypertension (BHT). Thirty-five patients were randomly allocated in two groups undergoing acute saline infusion (0.40 ml/min/kg for 45 min and 0.15 ml/min/kg for 75 min)before and after a 7-day period of treatment with either placebo or captopril at the dose of 12.5 (LD-CAP) or 50 mg (HD-CAP) twice a day. At baseline the effects of LD-CAP were limited to an increase in PRA and to a decrease in plasma aldosterone whereas HD-CAP decreased systolic and diastolic blood pressure (SBP, DBP), forearm vascular resistance (FVR) and increased venous distensibility (VV(30)) as well. After saline loading patients treated with HD-CAP showed an increase in SBP, DBP not observed in patients allocated to LD-CAP. Urinary sodium excretion in response to NaCl loading was selectively enhanced by LD-CAP (+25%) whereas HD-CAP did not (+6.3%). The present data suggest that low-doses of ACE-inhibitors acting through a selective blockade of RAA not associated with hemodynamic changes can enhance the natriuretic response to acute volume expansion in borderline hypertensives.

Adult↗

Factors associated with the development of stable hypertension in young borderline hypertensives.

OBJECTIVES: To identify factors predisposing subjects to the development of stable hypertension and to estimate their relative importance in 70 young patients with borderline hypertension monitored for 10 years. DESIGN: Longitudinal evaluation of the incidence of stable hypertension [diastolic blood pressure (DBP) > 95 mmHg]. METHODS: Patients were examined at baseline by determination of resting blood pressure, intracellular sodium level and individual pressor response to mental arithmetic and to intravenous saline loading. They were re-examined after 10 years to assess the prevalence of established hypertension and the importance of some prognostic variables identified prospectively (age, sex, intracellular sodium level, baseline blood pressure, pressor response to stress and acute salt-sensitivity). RESULTS: The prevalence of sustained hypertension (DBP > 95 mmHg) was 35.8% after 10 years of follow-up study. Subjects developing hypertension were older (26.9 +/- 1.3 versus 21.0 +/- 1.8 years) and showed a higher percentage of family history of hypertension (92 versus 64%) and of acute salt-sensitivity (72 versus 53%). The pressor response to mental arithmetic was greater in patients who developed hypertension (systolic blood pressure 26.9 +/- 1 versus 22.7 +/- 0.9 mmHg, P = 0.005 DBP = 16.6 +/- 0.8 versus 13.1 +/- 0.7 mmHg, P = 0.005), who also showed higher levels of intracellular sodium (30.7 +/- 0.6 versus 27.3 +/- 0.5 mmol/kg, P = 0.001). The same variables were found to be related to the development of hypertension in a multivariate analysis and the concomitant presence of 4-5 risk factors was associated with a reasonable predictive power for the identification of patients at high risk (sensitivity 72%, specificity 67%, predictive accuracy 76%). CONCLUSIONS: The present study demonstrates that borderline hypertensives at high risk of stable hypertension can be identified by the concomitant evaluation of some clinical and cellular characteristics directly related to long-term development of high blood pressure.

Adult↗

Nitrendipine treatment in women with polycystic ovarian syndrome: evidence for a lack of effects of calcium channel blockers on insulin, androgens, and sex hormone-binding globulin.

It has been shown that in vitro calcium channel blockers may regulate insulin secretion, and in vivo studies have demonstrated that they can reduce the degree of hyperinsulinemia and ameliorate the insulin-resistant state in subjects (particularly men) with obesity and hypertension. It is also commonly accepted that hyperinsulinemia may be an important factor responsible for the development of hyperandrogenism in obese women with polycystic ovarian syndrome (PCOS). We, therefore, investigated whether the administration of nitrendipine, a widely used calcium channel blocker, may improve both insulin levels and hyperandrogenism in a group of seven insulin-resistant hyperinsulinemic women with obesity and PCOS. They were treated for 7-8 days with oral nitrendipine (10 mg, twice daily) or placebo using a double blind, cross-over design. Before and after treatment, blood samples were obtained for androgen and sex hormone-binding globulin determinations, and an oral glucose tolerance test was performed, measuring glucose and insulin. Both nitrendipine and placebo failed to decrease basal and stimulated insulin levels. Moreover, no significant variations in testosterone, dehydroepiandrosterone sulfate, or sex hormone-binding globulin concentrations were observed after either treatment. Therefore, these data fail to support previous suggestions that calcium channel blockers may play a role in the treatment of hyperandrogenism and hyperinsulinemia in obese women with PCOS.

Adult↗

Insulin regulates testosterone and sex hormone-binding globulin concentrations in adult normal weight and obese men.

There are no studies in vivo on the effects of insulin on androgens and sex hormone-binding globulin (SHBG) in men. We, therefore, investigated the effects of insulin suppression on testosterone and SHBG in two groups of eight nondiabetic adult obese men and six healthy normal weight men who underwent diazoxide treatment (100 mg, three times daily) for 7 days. Blood samples for hormone determination were obtained before the subjects had been selected for the study, immediately before diazoxide administration, and on the last day of treatment. A 24-h oral glucose tolerance test was also performed for glucose, insulin, and C-peptide determinations before and on the last day of treatment. Only one subject experienced significant side-effects, and no significant changes in mean body weight were found during the treatment. Diazoxide administration worsened glucose tolerance in several subjects and reduced fasting and glucose-stimulated insulin levels by approximately 50% in both control and obese subjects. No significant difference was present between historical and pretreatment hormone values in either group. Moreover, there were no differences in pretreatment gonadotropin and SHBG concentrations between the two groups, whereas testosterone (free and total) levels were lower in the obese than in the control subjects. After diazoxide administration, testosterone (free and total) decreased slightly, but significantly, whereas LH and SHBG significantly increased in both groups. Diazoxide treatment increased estradiol levels in controls, but not in obese men. In conclusion, these results indicate that in vivo, insulin is capable of stimulating testosterone production and, simultaneously, of inhibiting SHBG concentrations in both normal weight and obese men.

Adult↗

[Physiopathology of vasovagal syncope: review of the most endorsed theories and recent findings].

Vasovagal syncope is associated with an abnormal reflex and the physiopathological mechanisms of the phenomenon overall are only partially known. Experimental and clinical studies suggest that the main factor which triggers the syncope is the brusque interruption of the alpha-adrenergic tone with marked, sudden peripheral vasodilation. Although documented, vagal hypertony, with consequent bradycardia and asystolia, is only occasional and is almost always a secondary phenomenon. The most commonly suggested cause of vasovagal syncope is a Bezold-Jarish reflex starting from the cardiac receptors in the walls of the ventricle, mediated by the paradoxical activation of afferent vagal fibres. However, recent studies are suggesting that there may be other pathogenetic mechanisms such as the paradoxical activation of the venous-atrial baroceptors and other "extracardiac" vascular receptors. The neuro-endocrine aspect of the vasovagal reaction is very complex and in spite of the many studies carried out on the catecholamine, renal-angiotensive system, arginine-vasopressin, and b-endorphine trends, there are still many points awaiting clarification. The response of the autonomous nervous system linked to age also require further research.

Age Factors↗

Erythrocyte Na+,K(+)-ATPase properties and adenylate energy charge in normotensives and in essential hypertensives.

The activity and some kinetic properties of RBC Na+,K(+)-ATPase (EC 3.6.1.37) were investigated in essential hypertensives (EH; 40 subjects) and normotensives (NT; 20 subjects). A decrease in ouabain-sensitive 86Rb uptake as well as ouabain-sensitive ATPase activity was found in EH. [Na+]i and [K+]i of EH did not show any statistical difference from NT. Na+,K(+)-ATPase showed a reduced Mg2+ activation and the apparent Km value for Mg2+ was 2-fold increased in the EH group. The influence of temperature on the Na+,K(+)-ATPase showed a reduced modulation and a minor activity peak at 37 degrees C in the patients, consequently the calculated activation energy of the enzyme was increased at temperatures lower than 40 degrees C. Increased RBC adenylate energy charge (EC) was observed in EH when compared with NT. A negative correlation between EC and total Na+,K(+)-ATPase activity was found when all subjects were compared and also in both groups, showing a possible pump involvement in the regulation of the RBC metabolic flux in EH. These data provide evidence about some modifications in active Na+,K+ transport and in EC in RBC which allows a further characterization of membrane cation fluxes in EH.

Adenine Nucleotides↗

Effects of new fish oil derivative on fatty acid phospholipid-membrane pattern in a group of Crohn's disease patients.

Fish oil has been recently proposed as a possible effective treatment in inflammatory bowel disease (IBD); however, a lot of annoying side effects (ie, belching, halitosis, diarrhea, etc) affect patient compliance. We carried out a study of patient tolerance in a group of Crohn's disease (CD) patients with a new fish oil derivative consisting of 500-mg capsules of eicosapentaenoic-docosahexaenoic (EPA 40%-DHA 20%), a free fatty acid mixture (Purepa), and we also evaluated its incorporation into phospholipids, both in plasma and in red cell membranes. Five groups of 10 CD patients in remission received nine Purepa capsules daily in four different preparations (A: uncoated, B: coated, pH 5.5; C: coated, pH 5.5, 60 min time release; D: coated, pH 6.9) and 12 x 1-g capsules daily of a triglyceride preparation (Max-EPA, EPA 18%-DHA 10%), respectively. We coated three of the four Purepa preparations in order to delay the release of contents in an attempt to minimize the side effects. After six weeks of treatment, the group taking Purepa capsules, coated, pH 5.5, 60 min time release (group C) showed the best incorporation of EPA and DHA in red blood cell phospholipid membranes (EPA from 0.2 to 4.4%, DHA from 3.7 to 6.3%), and no side effects were registered, whereas in all other groups side effects were experienced in 50% or more of subjects. This new preparation will make it possible to treat patients for long periods.

Adult↗

Measurement of steroid hormones in plasma by isocratic high performance liquid chromatography coupled to radioimmunoassay.

The study of steroidal profiles requires simultaneous determinations of various steroid hormones that cannot be appropriately carried out with the conventional routine immunoassays. Moreover, there are several trials for which the assessment of multiple steroids from a single serum sample is mandatory. In this paper we describe a procedure for simultaneously measuring steroid hormones using a unified solid phase extraction which allows the measurement of both unconjugated and conjugated steroids from 1 ml of sample and a combination of HPLC with isocratic elution followed by RIA. The entire procedure was preliminary carried out for the measurement of testosterone, dehydroepiandrosterone and its sulphated conjugate, androstenedione and 17 hydroxyprogesterone. The use of this technique allows precise and accurate measurements of steroid profile with a single serum aliquot and could be helpful in the diagnosis of various form of endocrine disorders.

Animals↗

Short report: zinc sulphate supplementation corrects abnormal erythrocyte membrane long-chain fatty acid composition in patients with Crohn's disease.

Patients with Crohn's disease may become zinc-deficient and, in such patients, an altered metabolism of radiolabelled long-chain fatty acids has been reported. We have investigated the possible reversal by zinc supplementation of altered long-chain fatty acid profiles of red cells in Crohn's disease. Twenty patients with long-standing Crohn's disease in clinical remission received 200 mg of zinc sulphate daily for 6 weeks. Phospholipid fatty acid profiles of washed red cells were analysed before and after zinc treatment and compared to those of 20 unsupplemented healthy controls. Plasma zinc levels in Crohn's were 72 +/- 8 micrograms/dL before zinc treatment and increased to 114 +/- 10 micrograms/dl after the therapy. Prior to zinc supplementation, the percentage of palmitic, stearic and oleic acids was significantly higher in Crohn's disease, while linoleic, arachidonic and n-3 fatty acids were reduced in Crohn's disease compared to healthy controls. Zinc supplementation abolished these pre-treatment differences in red-cell long-chain fatty acid profiles but did not affect plasma fatty acid values. Further studies are needed to clarify whether these fatty acid changes can be related to the clinical course of the disease.

Adult↗

Bioavailability of single and multiple doses of a new oral formulation of 5-ASA in patients with inflammatory bowel disease and healthy volunteers.

AIMS: An oral multiparticulate coated formulation of 5-aminosalicylic acid (5-ASA: mesalazine) has been developed to provide a controlled release of the drug, in a pH-dependent fashion, in the distal ileum and colon. The purpose of the present study was to assess the systemic availability of the drug and its metabolite, acetyl-5-ASA, following single (800 mg) and multiple (2400 mg for 56 days) oral dose administration. METHODS: Three groups were investigated: six healthy volunteers, six patients with ulcerative colitis, and nine patients with Crohn's disease in remission. In the single oral dose study (800 mg) all three groups participated, whereas in the multiple oral dose study (2400 mg/day for 56 days) only the patients with inflammatory bowel disease took part. Plasma and urine 5-ASA and Ac-5-ASA were measured for 48 h. RESULTS: In the single oral dose regimen, systemic absorption of 5-ASA and Ac-5-ASA were low and did not differ between the three groups. Only about 20% of the 5-ASA given was absorbed, with more than 80% of the drug being available in the terminal ileum and colon for therapeutic activity. The multiple oral dose regimen in patients with inflammatory bowel disease produced a significantly higher plasma concentration and urine excretion of both 5-ASA and Ac-5-ASA by the end of the treatment, in comparison to the first dose. There was a statistically higher systemic absorption of 5-ASA in patients with ulcerative colitis than in patients with Crohn's disease. After 56 days of dosing, no adverse event was reported and laboratory screening tests remained within normal ranges. CONCLUSIONS: The new oral 5-ASA formulation is gradually released throughout the small and large intestine, reflected by a low plasma concentration of the drug and its metabolite, with about 80% of the drug being available for ileum-colon therapeutic activity.

Administration, Oral↗

Influence of dental glove type on the penetration of liquid through experimental perforation: a spectrophotometric analysis.

This study was made to assess whether the physical structure or the commercial make of a glove has any influence on the penetration of liquid through perforations in the glove during work. A comparison was made between three types of gloves (10 for each brand name and type): vinyl (Peha Fit, Paul Hartmann), latex (without ASTM certification), and Biogel D (Regent Dental Division) for a total of 30 gloves. Of the 10 gloves for each type, five were worn tightly adhering to the operator's hand and five were worn relatively loosely. Holes of a predetermined size (0.40 mm) were made in each glove on the index, middle, and ring fingers, for a total of 90 holes. A randomized preprogrammed list ensured a perfect balance of the three variables: type of glove, adherence to the hand, and fingers having holes. The amount of liquid that penetrated the gloves through the holes was determined by placing the gloved hand in a tank containing a colored substance for 3 minutes and then analyzing the colored substance that had penetrated the glove with an ultraviolet (UV) spectrophotometer. The results clearly showed that the amount of liquid that penetrated through the holes varied significantly (p < 0.001) according to the type of glove tested. The mean quantity of liquid penetrating the vinyl gloves (6.24 microL) was approximately five times higher than that of the latex gloves (1.20 microL), and 100 times higher than that of the Biogel D gloves (0.05 microL). The statistical differences between the three types of gloves were even more significant in the cases in which the glove adhered closely to the hand (12.44 microL in vinyl, 2.37 microL in latex, and 0.09 microL in Biogel D), whereas no significant difference was found when the gloves were loose (0.03 microL in vinyl, 0.04 microL in latex, and 0.00 microL in Biogel D).

Analysis of Variance↗