The induction of epidermal ornithine decarboxylase following tape stripping is inhibited by a topical vitamin D3 analogue (MC903)

The efficacy of MC903, a vitamin D3 analogue, in reducing hyperproliferation as determined by levels of ornithine decarboxylase (ODC) was investigated in a double-blind study of 15 patients with chronic plaque psoriasis. The lesions of psoriasis were treated for 8 weeks with MC903 in one of two different cream bases or with a placebo cream. Biopsies were taken before and after treatment. In addition an uninvolved area of skin was treated during the last 3 weeks and this as well as control areas were then sellotape stripped and biopsied after 8 h. Clinical improvement was seen in eight out of 11 patients treated with MC903 but there was no reduction in the level of ODC in psoriatic lesions after 8 weeks of treatment. The levels of ODC in the tape-stripped uninvolved skin after 3 weeks of treatment with MC903 averaged 22.5 +/- 4.2 pmol/min/mg protein as compared to 58.6 +/- 12.6 pmol/min/mg protein (P = 0.004). The trauma-induced induction of ODC activity was markedly inhibited by the application of MC903.     

Successful pregnancy in primary glomerular disease

The course of 66 pregnancies was studied in 48 women with primary glomerular diseases. In all cases diagnoses were established by biopsy before pregnancy. They were: membranoproliferative glomerulonephritis in 16 patients, focal glomeruloesclerosis in 13, IgA nephropathy in 10, membranous nephropathy in seven and focal glomerulonephritis in two women. The clinical status of the nephropathy before conception was that 43 had only mild renal dysfunction, five had moderate renal insufficiency, serum creatinine (1.3 to 1.9 mg%), eight women had hypertension (150/100 mm Hg) and eight had nephrotic range proteinuria. Their clinical course was compared with a control group of 36 women with primary glomerular disease who did not become pregnant, and were matched for similar age, histological type, and status of nephropathy (renal function, blood pressure and proteinuria). After one year and at the end of the five year follow-up period, the incidence of hypertension, proteinuria, and renal failure was similar in the two groups. The fetal survival rate was 92%; 51 pregnancies ended in full-term delivery, with a mean birthweight of 3,242 +/- 320 g. There were seven pre-term deliveries (2,170 +/- 135 g), three small for gestational-age (2,340 +/- 135 g), two stillbirths and three spontaneous abortions. These patients had more pre-term deliveries (10.6%) and perinatal mortality (31%) than a normal population (5.5% and 9.6%, respectively). Blood pressure increased during pregnancy in 13 women; in 10 it was reversible, and in four it persisted after delivery. Ten gravidas developed increased proteinuria (reversible in six of them) and two others developed permanent impairment of renal function.(ABSTRACT TRUNCATED AT 250 WORDS)     

Expression of CD35 (CR1) and CD11b (CR3) on circulating neutrophils and eosinophils from allergic asthmatic children

Complement receptors on neutrophils and eosinophils play a role in activation and adhesion. During asthmatic reactions these receptors have been found elevated on circulating granulocytes. In the present study we compared the expression of CD35 (complement receptor type 1) and CD11b (complement receptor type 3) on neutrophils and eosinophils from asthmatic and non-asthmatic children. This was done in whole blood samples using depolarized light scattering for the discrimination of neutrophils and eosinophils. The non-stimulated expression as well as the upregulated expression of receptors by the chemotactic peptide N-formylmethionyl-leucyl-phenyl-alanine (fMLP) were studied. The results showed that without prior stimulation only the expression of CD35 on neutrophils was significantly elevated in children with asthma (P<0.05). After up-regulation with fMLP, the CD11b expression on neutrophils (P<0.005, fMLP: 0.002 microM) and eosinophils (P<0.05, fMLP: 0.02 microM) was significantly higher in asthmatic children than in the controls. These results indicate that the inducible expression of CD11b on neutrophils and eosinophils from allergic asthmatic children is primed in vivo.     

Embolization of nonvariceal portosystemic collaterals in transjugular intrahepatic portosystemic shunts

Percutaneous embolization of large portosystemic collaterals was performed in three patients following placement of a transjugular intrahepatic portosystemic shunt in order to improve hepatopetal portal flow. Improved hepatic portal perfusion was achieved in these cases, thereby theoretically reducing the risk of chronic hepatic encephalopathy.     

Small Cytoplasmic Antigens from Pseudomonas aeruginosa Stimulate γδ T Lymphocytes

γδ T lymphocytes respond to different bacterial antigens and transformed cells. The antigenic molecules responsible for this activity have been studied extensively in antigenic preparations from Mycobacterium . We describe here the in vitro effect of Pseudomonas aeruginosa on γδ T lymphocytes and the properties of the implicated compounds. We found a preferential γδ T-cell expansion when we used heat-treated P. aeruginosa preparations and a dose-dependent inhibition of proliferation of peripheral blood mononuclear cells (PBMC) when non-heat-treated antigens were studied. This expansion corresponded to a Vγ9-positive subpopulation. In contrast to αβ T lymphocytes, the highest stimulatory activity was restricted to very small cytosolic compounds. This activity was protease resistant and phosphatase sensitive and always dependent on interleukin (IL)-2 or αβ T-cell activation. We concluded that the antigenic molecules from P. aeruginosa that activated γδ T lymphocytes were small, non-peptidic, phosphorylated compounds, similar to those previously described from Mycobacterium .     

Arachidonic acid metabolites in CSF in hypoxic-ischaemic encephalopathy of newborn infants

The aim of this study was to evaluate the cerebral synthesis of eicosanoids in the asphyctic newborn and to investigate the relation between the prostanoid profiles in cerebrospinal fluid (CSF) and the appearance and severity of hypoxic-ischaemic encephalopathy (HIE). Levels of 6-keto-PGF _1-α, TXB₂, PGE₂ and PGF_2-α in CSF were measured in 40 full term newborns during the first day of life. Thirty of these newborns had birth asphyxia and were divided into three groups: 10 without HIE, 12 with mild HIE and 8 with moderate-severe HIE. They were compared to a control group of 10 non-hypoxic newborns. Determinations of the metabolites in CSF were performed by RIA and expressed as pg/ml (mean ± SD). The CSF TXB₂ (thromboxane A₂ metabolite) in asphyxiated newborns was always higher than in the control group (28.12 ± 10.6), and related to the severity of HIE ( p = 0:005): without HIE (50.84 ± 16.4; p = 0:02), mild HIE (80.65 ± 12.64; p ± 0:01) and moderate-severe HIE (178.14 ± 20.5; p < 0:01). The CSF 6-keto-PGF _1-α (prostacyclin metabolite) in asphyxiated newborns was always higher than in the control group (80.55 ± 12.56), but indirectly related to the severity of HIE: without HIE (240.95 ± 28.12; p < 0:01), mild HIE (183.65 ± 30.1; p < 0:01) and moderate-severe HIE (140.55 ± 25.12; p < 0:01). In the moderate-severe HIE group, the increase in TXB₂ was higher than the rise in 6-keto-PGF _1-α.     

Isoquinoline Derivatives Isolated from the Fruit of Annona muricata as 5-HTergic 5-HT1A Receptor Agonists in Rats: Unexploited Antidepressive (Lead) Products

The fruit and the leaves of Annona muricata (Annonaceae) are used in traditional medicine for their tranquillizing and sedative properties. Extracts of the plant have been shown to inhibit binding of [³H]rauwolscine to 5-HTergic 5-HT_1A receptors in calf hippocampus, and three alkaloids, annonaine ( 1 ), nornuciferine ( 2 ) and asimilobine ( 3 ), isolated from the fruit have been shown to have IC50 values of 3 μm , 9 μm and 5 μm , respectively, although in ligand-binding studies it was not possible to determine whether interaction of these ligands with the receptor was agonistic or antagonistic. This paper presents the results of functional assays of the alkaloids. The inhibition of cAMP accumulation was tested in NIH-3T3 cells stably transfected with the 5-HT_1A receptor from man. None of the alkaloids showed antagonistic properties towards the 5-HT_1A receptors because in the antagonistic tests no influence on the forskolin-stimulated increase of cAMP level was detected. Full agonistic properties were measured for all three compounds; the inhibition constants (K_i) for 1, 2 and 3 were < 10 μm . Inhibition of the binding of the radioligand to the 5-HT_1A receptor was observed in every ligand-binding assay performed with the alkaloids; the K_i values for 1, 2 and 3 were in the μm range. These results imply that the fruit of Annona muricata possesses anti-depressive effects, possibly induced by compounds 1, 2 and 3 , and that in the past potent leads for the development of anti-depressive therapeutics have not been used.     

Prospective study of antigenemia,plasma viremia and lymphocytic viremia in HIV-infected hemophiliacs

A total of 186 blood samples from 24 HIV-1 seropositive hemophiliac patients, monitored every four months for 29 months, were investigated for the presence of viral antigen in plasma. In addition, peripheral blood mononuclear cells (PBMC) were cultured for HIV-1, using normal PBMC as a target for replication. Antigenemia was detected in 51 % of the patients and from PBMC in 87.5 % of the patients. The incidence of HIV isolation in asymptomatic patients (42.8 %) was similar to that found in symptomatic patients (51.4 %). Patients with opportunistic infections had a higher incidence of lymphocytic viremia (p<0.05). Plasma viremia was closely associated (p<0.05) with low CD4+ counts and infection progression. The persistence of antigenemia was also a marker of a poor clinical course. In treated patients, plasma viremia was the marker that better correlated with the clinical course, and it did not appear during the first nine months of therapy. Zidovudine doses of >500 mg/day significantly lowered the appearance of antigenemia and lymphocytic viremia (p<0.05).