Liberation of prostaglandin-like substances from the isolated coronary artery in presence of angiotensin and of 4-methylesculetin

The aim of this work is to study the mechanism by which 4-Methylesculetin (4-ME) causes the relaxation or inhibits the Angiotensin II (ATN 2) induced contraction in the smooth muscle. The effect of 4-Me, alone or associated with Ascorbic Acid, on basal tone and ATN 2 induced contraction of isolated coronary strips have been studied. Experiments have been carried out in presence of Lysine Acetylsalicylate (LAS) and Indomethacin (IN), known inhibitors of prostaglandin-synthetase. Both LAS and IN decrease but not abolish, the 4-ME induced relaxation and suppressed the depressive effect of 4-ME on the ATN 2 dependent contraction. From R.I.A. tests results that 6-Keto PGF1 alpha (prostacyclines stable metabolite) concentration increased with the addition of 4-ME to the bath. 6-Keto PGF1 alpha concentration was drastically reduced after IN and LAS use. Therefore, it seems reasonable to conclude that 4-ME influence could be mediated by prostacyclines release in the smooth muscle.     

Sustained ventricular tachycardia in postinfarct ischemic heart disease: spontaneous polymorphism. Clinical, therapeutic and prognostic aspects

Spontaneous Polymorphism (SP) is present when at least two episodes of Sustained Ventricular Tachycardia (SVT) occur spontaneously in the same patient (pt) with different bundle branch block pattern or with shifting of QRS axis by greater than or equal to 90 in the various episodes. We undertook this study in order to investigate the clinical significance of SP in SVT as well as therapeutic and prognostic implications. MATERIAL AND METHODS. From our global pts populations we chose those with SVT in chronic ischemic heart disease (CIHD) with previous myocardial infarction (PMI), they had to be already studied by electrophysiologic technique (EES). The pts were divided into two groups (Gr.): Gr. I: 13 SP pts (12 M, 1 F, mean age 57.5 +/- 13; mean follow-up 19.2 +/- 11 months); Gr. II: 15 no SP pts (14 M, 1 F, mean age 60 +/- 10; mean follow-up 9.9 +/- 13 months). RESULTS: The two Gr. are comparable in terms of symptoms, exercise tolerance, infarct site, intraventricular conduction disturbances (61.5% and 66.6% respectively), ventricular wells kinetics (38.4% and 26.6% respectively) and time interval between acute myocardial infarction the first episode of SVT (7.58 +/- 6.02 and 8.27 +/- 6.57 years respectively). 8 of the 10 alive Gr. I pts have been treated with Amiodarone (A) (2800-4200 mg/wk). All 9 alive Gr. II pts are on A (1400-4200 mg/wk). A serum level in 7 Gr. I pts was 1.7 +/- 0.65 mcg/ml and 1.61 +/- 0.67 in 5 Gr. II pts. 3/13 Gr. I pts died: 2 for sudden death (15.3%), 6/15 Gr. II pts died: 4 suffered sudden death (26.6%).(ABSTRACT TRUNCATED AT 250 WORDS)     

Nucleotide sequence of estrogen receptor cDNA from Sprague-Dawley rat.

The cDNA of the Sprague-Dawley rat estrogen receptor was sequenced. With respect to the published Wistar rat estrogen receptor sequence, a single amino acid difference (tryptophan instead of asparagine) was found in the hormone binding site. Since tryptophan was found at the same position in chicken, human and mouse estrogen receptors, it is proposed that the Wistar rat could represent an interesting natural mutant for estrogen receptor studies.     

Primary microparticles and agglomerates of morphine for nasal insufflation

The aim of this work was to study the characteristics of powders of morphine HCl suitable for nasal administration to be employed for pain treatment as alternative to injection. Primary microparticles of morphine were prepared by spray drying of aqueous drug solutions using sugars or sugar derivatives as drying protectors and particle shapers. The spray drying procedure modified morphine crystallinity making the substance amorphous and affecting its stability in dependence on the excipient employed. A tendency of the spray-dried powders to turn to varying degrees of yellow was observed. Tumbling the powder in a rotating pan allowed the agglomeration of the primary microparticles. Agglomerates were also obtained by tumbling a mixture of morphine crystals and spray-dried microparticles of excipients, with advantages for the stability of the preparation. A nasal device quantitatively insufflated all the morphine agglomerates. The in vitro transport of morphine through rabbit nasal mucosa was faster using nasal powders than with the saturated solution of morphine. Lactose was the most effective excipient for agglomerate manufacturing and delivery of spray-dried morphine. The agglomerates of morphine crystals mixed with mannitol/lecithin microparticles showed superior stability. However, the drug permeation through rabbit mucosa was slower than with spray-dried morphine microparticle agglomerates.     

Recovery of the olfactory receptor neurons in the African Tilapia mariae following exposure to low copper level

Low levels of Cu(2+) are known to specifically cause olfactory neuron death in fish olfactory epithelium. This study investigated the morphological changes in the olfactory mucosa of the cichlid Tilapia mariae, after a 4-day exposure to different concentrations of Cu(2+) (20, 40 and 100 microg/l), and the regeneration time-frame, when fish exposed to 20 microg/l were returned to dechlorinated tap water. Light microscopy, combined with Fluoro Jade-B staining, permitted the observation of a dose-dependent damage which became less severe and more circumscribed to receptor cells when Cu(2+) concentration decreased. The regeneration process in the olfactory tissue was examined in fish after 0, 3, and 10 days of recovery in well water. Immunostaining with PCNA showed a massive mitotic activity in the basal region of the mucosa immediately after exposure was terminated. The mitotically produced elements were immature neurons since they expressed the neural growth-associated phosphoprotein GAP-43. After 3 days of recovery the nuclei had already completed their migration to the upper portion of the epithelium and mitotic activity was much less intensive. After 10 days the olfactory tissue did not present differences when compared to the control tissue. These results suggest that after 10 days the regeneration is completed and the integrity of the tissue restored.     

Prognostic value of the Kiel classification of malignant non-Hodgkin's lymphomas.

The aim of the present research was to evaluate the prognostic value of the Kiel classification of malignant non-Hodgkin's lymphomas. For this purpose a series of 100 consecutive, previously untreated adults with advanced malignant non-Hodgkin's lymphomas was analyzed. The median age of the patients was 54 years; 61 patients were males. Although the number of the various groups considered was limited, a statistically significant difference (p less than 0.001) was found in the median survival of patients with lymphomas of low-grade malignancy (lymphocytic, lymphoplasmacytoid, centrocytic, centroblastic-centrocytic lymphoma) and lymphomas of high-grade malignancy (centroblastic, lymphoblastic, immunoblastic lymphoma). A difference in survival (p less than 0.001) was also observed among the patients with lymphocytic lymphoma and those with centroblastic-centrocytic lymphoma, whereas no significant difference in survival was found between the histological subtypes of high-grade malignant lymphomas. Our observations support the opinion that the Kiel classification is useful in clinical practice to distinguish the histological types with a better prognosis from those with a worse one; in addition this classification appears to be of conceptual value.     

The progression from obesity to type 2 diabetes in Alström syndrome

Bettini V, Maffei P, Pagano C, Romano S, Milan G, Favaretto F, Marshall JD, Paisey R, Scolari F, Greggio NA, Tosetto I, Naggert JK, Sicolo N, Vettor R. The progression from obesity to type 2 diabetes in Alström syndrome. Background: Alström syndrome (ALMS) is a rare autosomal recessive monogenic disease associated with obesity, hyperinsulinemia, and alterations of glucose metabolism that often lead to the development of type 2 diabetes at a young age. Objective: To study the relationship between weight and metabolism in a group of ALMS patients and matched controls. Research design and methods: Fifteen ALMS patients (eight males, seven females; aged 3–51) were compared in a cross‐sectional study with an age‐ and weight‐matched control population. Anthropometric parameters, fat mass, glucose and insulin secretion in basal and dynamic oral glucose tolerance test (OGTT) conditions were measured. Furthermore, anthropometric and body composition data were obtained from an international group of 27 ALMS patients (13 males, 14 females, age range: 4–29 yr). Results: In ALMS we observed an inverse correlation between age and standard deviation scores for height, weight, and body mass index. The OGTT glycemic curves of ALMS subjects were similar to those of age‐matched controls, whereas insulin response was clearly greater. In ALMS individuals the insulin response showed a reduction with age. We documented pathologic values of the derived indices homeostasis model assessment of insulin resistance (HOMA‐IR), insulin sensitivity index, HOMA%β‐cell and insulinogenic index in ALMS, but unlike the insulin‐resistance indices, the β‐cell function indices showed a significant reduction with age. Conclusions: In ALMS the progression from the early onset obesity toward the impaired fasting glucose or impaired glucose tolerance and overt diabetes is mostly because of a progressive failure of β‐cell insulin secretion without any further worsening of insulin resistance with age, even in the presence of weight reduction.     

Hydroxylation of D-phenylalanine as a novel approach to detect hydroxyl radicals: application to cardiac pathophysiology

OBJECTIVE: Research in the pathophysiology of ischemia/reperfusion or redox signaling is hindered by lack of simple methodology to measure short-lived oxygen radicals. In the presence of hydroxyl radical ((*)OH), d-phenylalanine (d-Phe) yields para-, meta- and ortho-tyrosine. We have previously demonstrated that d-Phe can accurately detect (*)OH formation in chemical, enzymatic and cellular systems by simple HPLC methodology [Anal Biochem 290:138;2001]. In the present study, we tested whether d-Phe hydroxylation can be used to detect (*)OH formation in intact organs. METHODS: Rat hearts were perfused with buffer containing 5 mM d-Phe and subjected to 30 min of total global ischemia at 37 degrees C followed by 45 min of reperfusion. Quantitative analysis of the three hydroxytyrosine isomers was achieved by HPLC-based electrochemical detection of cardiac venous effluent, with the analytical cells operating in the oxidative mode. The detection limit of this assay was <10 fmol. RESULTS: Under baseline conditions, hydroxytyrosine release from the heart was very low ( congruent with0.8 nmol/min/g). However, a prominent tyrosine burst occurred immediately upon post-ischemic reflow. In cardiac effluent collected 40 s into reperfusion, the hydroxytyrosine concentration was more than 40 times greater than at baseline; hydroxytyrosine concentration then progressively declined, to return to pre-ischemic values by 5 min of reperfusion. In parallel experiments, formation of hydroxytyrosines was markedly reduced in hearts reperfused in the presence of the (*)OH scavenger mannitol. Inclusion of 5 mm d-Phe in the perfusion medium altered neither basal cardiac function nor coronary vascular tone, but it enhanced recovery of myocardial function during post-ischemic reperfusion, consistent with direct reaction with (*)OH. CONCLUSION: Our results demonstrate that d-Phe is a sensitive method for detection of (*)OH generation in the heart. Since d-Phe is not a substrate for endogenous enzymes, it can be exploited as a reliable method to measure (*)OH formation under a variety of pathophysiological conditions.