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Biomedical subjects

A Wolf

Publications and source records attributed to A Wolf.

At least 127 records · Page 7Linked to original sources
PubMed1998

Comparative study of cyclosporin A, cyclosporin G, and the novel cyclosporin derivative IMM 125 in isolated glomeruli and cultured rat mesangial cells: a morphometric analysis.

BACKGROUND: One adverse side-effect of the immunosuppressive drug cyclosporin A (CsA) is a decrease in glomerular filtration rate (GFR). This effect might be the result of increased glomerular contractions. The present study compared the contractile effects of CsA, cyclosporin G (CsG) and the novel cyclosporin derivative IMM 125 in isolated rat glomeruli and primary cultures of rat mesangial cells. METHODS: Interactive image analysis was used to measure glomerular and mesangial cell contraction. RESULTS: CsA, CsG, and IMM 125 at concentrations of 0, 10(-9), 10(-8), 10(-7), 10(-6) and 10(-5) M caused a time-dependent and a concentration-dependent contraction of isolated glomeruli and mesangial cells 30 min after incubation. In glomeruli, CsA was more potent than CsG and IMM 125. In mesangial cells, IMM 125 also exhibited the lowest contractile activity, while CsA and CsG were almost equally myoreactive. The absolute degree of the glomerular contraction was proportional to the number of contracting mesangial cells in one glomeruli. The number of responding cells after incubation with IMM 125 and CsG were lower compared to CsA, which might explain the different response with CsG and CsA in both models. CONCLUSIONS: Since the concentrations used in these experiments were close to that reached in rat serum after treatment with CsA, the present results suggest that the contractile effects of IMM 125 and CsG in isolated glomeruli were clearly smaller compared to CsA, which might reflect the cyclosporins induced GFR changes in vivo.

Animals↗
PubMed1998

The never ripe mutant provides evidence that tumor-induced ethylene controls the morphogenesis of agrobacterium tumefaciens-induced crown galls on tomato stems

We confirm the hypothesis that Agrobacterium tumefaciens-induced galls produce ethylene that controls vessel differentiation in the host stem of tomato (Lycopersicon esculentum Mill.). Using an ethylene-insensitive mutant, Never ripe (Nr), and its isogenic wild-type parent we show that infection by A. tumefaciens results in high rates of ethylene evolution from the developing crown galls. Ethylene evolution from isolated internodes carrying galls was up to 50-fold greater than from isolated internodes of control plants when measured 21 and 28 d after infection. Tumor-induced ethylene substantially decreased vessel diameter in the host tissues beside the tumor in wild-type stems but had a very limited effect in the Nr stems. Ethylene promoted the typical unorganized callus shape of the gall, which maximized the tumor surface in wild-type stems, whereas the galls on the Nr stems had a smooth surface. The combination of decreased vessel diameter in the host and increased tumor surface ensured water-supply priority to the growing gall over the host shoot. These results indicate that in addition to the well-defined roles of auxin and cytokinin, there is a critical role for ethylene in determining crown-gall morphogenesis.

Journal Article↗
PubMed1998

Hepatocellular effects of cyclosporine A and its derivative SDZ IMM 125 in vitro.

The novel immunosuppressive drug O-hydroxyethyl-D(Ser)8-cyclosporine (SDZ IMM 125) and cyclosporine A (CyA) were compared in different in vitro models with respect to hepatocellular side effects. SDZ IMM 125 was less lipophilic than CyA and also decreased liposomal membrane anisotropy less. Furthermore, SDZ IMM 125 increased Na+ and Ca++ permeability across the liposomal membranes significantly more than CyA. The uptake of CyA and SDZ IMM 125 into freshly isolated rat hepatocytes was neither saturable, Na+ dependent or temperature sensitive, nor could it be inhibited vice versa, indicating passive diffusion. The diffusion coefficient of CyA was about two times higher than that of SDZ IMM 125, reflecting its higher lipophilicity. In primary hepatocyte monolayers the cellular concentrations of CyA were about two times higher than that of SDZ IMM 125. As an indicator of cholestasis the saturable uptake of cholyltaurine into isolated cells was found to be apparently competitively inhibited to the same extent by both compounds. In isolated perfused rat livers SDZ IMM 125 caused a significantly greater decrease in bile flow than did CyA. Release of lactate dehydrogenase from hepatocyte primary cultures and from isolated perfused livers were determined as parameter of cell damage. In both systems the cytotoxicity of SDZ IMM 125 was significantly higher than that of CyA. The data suggest that SDZ IMM 125 causes greater cholestatic and cytotoxic effects than CyA at equimolar cellular exposure.

Animals↗
PubMed1998

Differential contribution of angiotensinergic and cholinergic receptors in the hypothalamic paraventricular nucleus to osmotically induced AVP release.

We studied the involvement of periventricular and hypothalamic angiotensinergic and cholinergic pathways in osmotically induced arginine vasopressin (AVP) release into the blood. In conscious Wistar rats, i.c.v. injections of 0.2, 0.3 and 0.6 M hyperosmolar saline (5 microl) resulted in concentration-dependent increases in AVP release (5.2 +/- 1.5, 10.6 +/- 2.2 and 18.0 +/- 2.2 pg/ml, respectively, vs. 2.0 +/- 0.1 in controls). The two lower saline concentrations did not affect arterial blood pressure (non-pressure-associated AVP release), whereas 0.6 M saline induced increase in blood pressure (pressure-associated AVP release). In the first set of experiments, periventricular angiotensin AT1, muscarinic or nicotinic receptors were blocked by i.c.v. administration of losartan (10 nmol), atropine (100 nmol) or hexamethonium (100 nmol), respectively, before i.c.v. hyperosmolar saline injections. Losartan significantly reduced the 0.2 M and 0.3 M, but not the 0.6 M, saline-induced increase in AVP release. The 0. 3 M saline-induced AVP release was blocked by atropine and hexamethonium, whereas the 0.6 M saline-induced AVP release was blocked by atropine only. In the second set of experiments, losartan (4 nmol), atropine (200 nmol) or hexamethonium (200 nmol) was injected bilaterally into the paraventricular nucleus before i.c.v. hyperosmolar saline injections. Losartan reduced 0.3 M and potentiated 0.6 M saline-induced AVP release. On the other hand, atropine and hexamethonium significantly reduced both 0.3 and 0.6 M saline-induced AVP release. We conclude that afferents arising from periventricular osmosensitive neurons to the hypothalamic paraventricular nucleus, which are involved in non-pressure-associated osmotically induced AVP release, are both angiotensinergic and cholinergic, whereas those mediating pressure-associated AVP release are cholinergic in nature.

Angiotensin Receptor Antagonists↗
PubMed1998

Sensitivity of hypothalamic paraventricular nucleus to C- and N-terminal angiotensin fragments: vasopressin release and drinking.

We studied the effect of angiotensin (ANG) peptides and their C- and N-terminal fragments, microinjected bilaterally into the hypothalamic paraventricular nucleus (PVN) of male Wistar rats, on arginine vasopressin (AVP) release into the blood and drinking. ANG II (1-8) and the C-terminal ANG III (2-8) at 0.1-100 pmol/200 nl induced a dose-dependent increase in AVP release with a maximum of 26.45+/-6.0 and 31.86+/-7.0 pg/ml, respectively, vs 1.6+/-2.0 pg/ml in vehicle treated controls (P<0.001). The highest dose of ANG II and ANG III also induced drinking responses of 4.3+/-0.78 and 2.91+/-0.54 ml water/15 min, respectively. Bilateral pretreatment of the PVN with the AT1 receptor antagonist losartan (4 nmol/200 nl) inhibited ANG II- and ANG III-induced AVP release and drinking. Different doses of the C-terminal ANG IV (3-8), ANG (4-8) or ANG (5-8) peptides did not induce AVP release or drinking. The N-terminal ANG (1-7) peptide induced a dose-dependent increase in AVP release (maximum 8.5+/-3.5 pg/ml after 100 pmol) but the effect was much less potent than that induced by the same dose of ANG II or ANG III. ANG (1-7) failed to induce a drinking response. Pretreatment of the PVN with losartan or the AT2 receptor antagonist, PD 123177 (4 nmol/200 nl), inhibited the 100 pmol ANG (1-7)-induced AVP release. The N-terminal ANG (1-4) peptide did not affect AVP release or drinking at any dose tested. Our data demonstrate that the C-terminal ANG II (1-8) and ANG III (2-8), but not shorter fragments, can induce AVP release and drinking response via AT1 receptors in the PVN. The N-terminal ANG (1-7) was less potent in stimulating AVP release than ANG II or ANG III and had no influence on drinking. Thus, the presence of both arginine2 and phenylalanine8 in the angiotensin peptide sequence appears to be important to elicit AVP release and drinking from the PVN in vivo.

Angiotensin II↗
PubMed1997

Proteolytic activation of cholera toxin and Escherichia coli labile toxin by entry into host epithelial cells. Signal transduction by a protease-resistant toxin variant.

Cholera and Escherichia coli heat-labile toxins (CT and LT) require proteolysis of a peptide loop connecting two major domains of their enzymatic A subunits for maximal activity (termed "nicking"). To test whether host intestinal epithelial cells may supply the necessary protease, recombinant rCT and rLT and a protease-resistant mutant CTR192H were prepared. Toxin action was assessed as a Cl- secretory response (Isc) elicited from monolayers of polarized human epithelial T84 cells. When applied to apical cell surfaces, wild type toxins elicited a brisk increase in Isc (80 microA/cm2). Isc was reduced 2-fold, however, when toxins were applied to basolateral membranes. Pretreatment of wild type toxins with trypsin in vitro restored the "basolateral" secretory responses to "apical" levels. Toxin entry into T84 cells via apical but not basolateral membranes led to nicking of the A subunit by a serine-type protease. T84 cells, however, did not nick CTR192H, and the secretory response elicited by CTR192H remained attenuated even when applied to apical membranes. Thus, T84 cells express a serine-type protease(s) fully sufficient for activating the A subunits of CT and LT. The protease, however, is only accessible for activation when the toxin enters the cell via the apical membrane.

Bacterial Toxins↗
PubMed1997

Mammalian homologues of the Polycomb-group gene Enhancer of zeste mediate gene silencing in Drosophila heterochromatin and at S. cerevisiae telomeres.

Gene silencing is required to stably maintain distinct patterns of gene expression during eukaryotic development and has been correlated with the induction of chromatin domains that restrict gene activity. We describe the isolation of human (EZH2) and mouse (Ezh1) homologues of the Drosophila Polycomb-group (Pc-G) gene Enhancer of zeste [E(z)], a crucial regulator of homeotic gene expression implicated in the assembly of repressive protein complexes in chromatin. Mammalian homologues of E(z) are encoded by two distinct loci in mouse and man, and the two murine Ezh genes display complementary expression profiles during mouse development. The E(z) gene family reveals a striking functional conservation in mediating gene repression in eukaryotic chromatin: extra gene copies of human EZH2 or Drosophila E(z) in transgenic flies enhance position effect variegation of the heterochromatin-associated white gene, and expression of either human EZH2 or murine Ezh1 restores gene repression in Saccharomyces cerevisiae mutants that are impaired in telomeric silencing. Together, these data provide a functional link between Pc-G-dependent gene repression and inactive chromatin domains, and indicate that silencing mechanism(s) may be broadly conserved in eukaryotes.

Amino Acid Sequence↗
PubMed1997

Dietary L-arginine supplementation normalizes platelet aggregation in hypercholesterolemic humans.

OBJECTIVES: The present study was designed to test the hypothesis that long-term dietary supplementation with the nitric oxide precursor L-arginine would enhance vascular or platelet-derived nitric oxide activity, or both, and thereby inhibit platelet reactivity in hypercholesterolemic humans. BACKGROUND: We have shown that reduced vascular activity of nitric oxide in hypercholesterolemic rabbits can be restored by L-arginine supplementation. The improvement in nitric oxide activity is associated with an inhibition of platelet aggregation ex vivo. This effect is most likely due to increased elaboration of endothelium- or platelet-derived nitric oxide, or both, because the inhibition of platelet reactivity was associated with elevation of intraplatelet cyclic guanosine monophosphate and was reversed by the nitric oxide synthase antagonist N-methyl-arginine. METHODS: In a double-blinded, randomized, placebo-controlled trial, hypercholesterolemic patients were assigned to L-arginine hydrochloride, 8.4 g/day orally, or placebo for 2 weeks. Platelet-rich plasma was obtained for aggregometry induced by collagen (1 to 10 micrograms/ml) at four points: baseline, after 2 weeks of treatment, after a 2-week washout and after a long-term washout of 16 weeks on average. Aggregation was quantified by light transmittance and expressed as a percent transmittance observed with platelet-poor plasma. RESULTS: Compared with normocholesterolemic control subjects, platelets from hypercholesterolemic subjects stimulated with 5 micrograms/ml of collagen showed increased aggregability (68.6% in hypercholesterolemic patients vs. 54.5% in normocholesterolemic control subjects, p < or = 0.02). After 2 weeks of treatment with L-arginine (but not placebo), platelet reactivity was modestly reduced; this effect persisted for 2 weeks after discontinuation of arginine (52.6% in arginine-treated patients vs. 65.1% in normocholesterolemic control subjects, p = 0.07). After 18 weeks (i.e., 16 weeks after discontinuing arginine treatment), the platelets of hypercholesterolemic patients once again became hyperaggregable, and the extent of platelet aggregation was significantly increased compared with the 4-week point (73.6% after vs. 52.6% during arginine treatment, p < 0.01). No significant change in platelet reactivity was seen in placebo-treated hypercholesterolemic patients throughout the study. L-Arginine treatment was well tolerated without side effects. CONCLUSIONS: This double-blinded, placebo-controlled study demonstrates that dietary supplementation with L-arginine can modestly attenuate the increased platelet reactivity seen in hypercholesterolemic patients. The data are consistent with our previous studies in hypercholesterolemic animals, demonstrating that L-arginine restores endogenous nitric oxide activity and inhibits platelet aggregation. Enhancement of endogenous nitric oxide activity is a potential novel therapeutic strategy worthy of further study.

Arginine↗
PubMed1997

Identification of HIV-1 determinants for replication in vivo.

Pathogenic organisms are frequently attenuated after long-term culture in vitro. The mechanisms of the attenuation process are not clear, but probably involve mutations of functions required for replication and pathogenicity in vivo. To identify these functions, a direct comparison must be made between attenuated genomes and those that remain pathogenic in vivo. In this study, we used the heterochimeric SCID-hu Thy/Liv mouse as an in vivo model to define human immunodeficiency virus type 1 (HIV-1) determinants which are uniquely required for replication in vivo. The Lai/IIIB isolate and its associated infectious molecular clones (e.g., HXB2) were found to infect T cell lines but failed to replicate in the SCID-hu Thy/Liv model. When a lab worker was accidentally infected by Lai/IIIB, however, HIV-1 was isolated only from infection of primary PBMC, and not from infection of T cell lines. We hypothesized that the lab worker was exposed to a heterogeneous viral stock which had been attenuated by passage in immortalized T cell lines. Either a rare family member from this stock was selected for in vivo replication or, alternatively, an attenuated genotype dominant in vitro may have reverted to become more infectious in vivo. To address this hypothesis, we have used the SCID-hu Thy/Liv model to study the replication of HXB2 and of HXB2 recombinant viruses with HIV-1 fragments isolated from the infected lab worker. HXB2 showed no or very low levels of replication in the Thy/Liv organ. Replacement of its subgenomic fragment encoding the envelope gene with a corresponding fragment from the lab worker isolate generated a recombinant virus (HXB2/LW) which replicated actively in SCID-hu mice. The NEF mutation in the HXB2 genome is still present in HXB2/LW. Thus, the LW sequences encode HIV-1 determinants which enhance HIV replication in vivo in a NEF-independent mechanism. The specific determinants have been mapped to the V1-V3 regions of the HIV-1 genome. Six unique mutations in the V3 loop region of HXB2/LW have been identified which contribute to the increased replication in vivo.

Amino Acid Sequence↗
PubMed1997

Enhancement of SDZ ICT 322-induced cataracts and skin changes in rats following vitamin E- and selenium-deficient diet.

The indole-3-carboxylic acid scopoine ester. SDZ ICT 322, is a selective hydroxytryptamine (5-HT3) antagonist, which after chronic treatment causes posterior subcapsular cataracts and skin changes such as hair loss, hyperaemia, desquamation and hyperkeratosis in rats. The detailed mechanisms underlying these changes are not yet known. In order to evaluate a possible oxidative stress-induced pathomechanism of SDZ ICT 322, the antioxidative defence capacity in rats was modulated by feeding a special vitamin E- and selenium-deficient (VE/SeD) diet. For this purpose 32 male Wistar rats, age 4 weeks, were pretreated for 8 weeks with either a VE/SeD diet or a normal standard diet. Each dietary group was divided into 8 control and 8 SDZ ICT 322-treated animals. SDZ ICT 322 was administered in feed to rats at an adjusted daily dose level of 125 mg/kg for 14 weeks. Plasma levels of SDZ ICT 322 as well as of the N-desmethyl metabolite were similar in rats fed the different diets in weeks 3, 6 and 14. In SDZ ICT 322 treated VE/SeD rats cataracts were observed by week 7, whereas in rats fed normal diet cataracts were first seen in week 14. In the normal dietary group no corneal opacity was found after SDZ ICT 322-treatment; however, a corneal opacity was seen in the deficiency group in parallel with one of the cataract animals in week 7. The incidence and severity of clinical skin signs were greater and their onset was earlier in the deficiency dietary group: onset occurred after 6 weeks compared to 9 weeks on the normal diet. Thiobarbituric acid reactive substances, an indicator mainly of oxidized lipids, were statistically significantly increased in the urine of rats administered SDZ ICT 322 and the VE/SeD diet. Uric acid, which is an endogenous antioxidant was statistically significantly decreased in the urine and plasma of SDZ ICT 322 VE/SeD treated rats. The clinical eye and skin changes occurring early after VE/SeD feeding, the unchanged drug plasma exposure and unchanged drug metabolite formation in combination with the general pro-oxidative activity of the drug suggest an oxidative stress-mediated pathomechanism of SDZ ICT 322 at high dose levels in rats.

Animals↗
PubMed1997

Silastic catheters for home antibiotic therapy in patients with cystic fibrosis.

UNLABELLED: Repeated 14-day courses of intravenous antibiotic therapy for patients with cystic fibrosis (CF), who have been colonized with Pseudomonas aeruginosa (PA), is one currently accepted treatment. Conventional intravenous cannulas for antibiotic delivery often have a short line life leading to frequent venipunctures. Therefore we used silastic catheters as a peripheral venous access. Silastic catheters (15 cm, 0.6 mm diameter) were inserted 10 cm into a cubital vein in 15 patients with CF (age 5-32 years) for 20 antibiotic courses. After the antibiotic infusion the catheter was flushed with 200 U heparin (2 ml Vetren). In all patients the antibiotic therapy was delivered as a home therapy. In 15 antibiotic courses the silastic catheter could be continuously used for 14 days. One patient with methicillin resistant Staphylococcus aureus received antibiotic therapy for 54 consecutive days using the same silastic catheter. The catheter had to be removed in four courses: once because of thrombophlebitis with local inflammation, once because of burning pain during infusion and occlusion twice. In one case the patient removed his catheter because of technical problems. No other serious side effects occurred. Ten patients had previously received intravenous antibiotics at least once. The median line life of the last used conventional peripheral cannula of all patients was 4 days versus 14 days with the use of the silastic catheter (P < 0.005). All patients preferred the silastic catheter to other venous access. CONCLUSION: Because of the long line life and easy handling, silastic catheters may be an alternative venous access to perform home antibiotic therapy in patients with CF.

Adolescent↗
PubMed1997

Effect of hydrostatic pressure on water penetration and rotational dynamics in phospholipid-cholesterol bilayers.

The effect of high hydrostatic pressure on the lipid bilayer hydration, the mean order parameter, and rotational dynamics of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) cholesterol vesicles has been studied by time-resolved fluorescence spectroscopy up to 1500 bar. Whereas the degree of hydration in the lipid headgroup and interfacial region was assessed from fluorescence lifetime data using the probe 1-(4-trimethylammonium-phenyl)-6-phenyl-1,3,5-hexatriene (TMA-DPH), the corresponding information in the upper acyl chain region was estimated from its effect on the fluorescence lifetime of and 3-(diphenylhexatrienyl)propyl-trimethylammonium (TMAP-DPH). The lifetime data indicate a greater level of interfacial hydration for DPPC bilayers than for POPC bilayers, but there is no marked difference in interchain hydration of the two bilayer systems. The addition of cholesterol at levels from 30 to 50 mol% to DPPC has a greater effect on the increase of hydrophobicity in the interfacial region of the bilayer than the application of hydrostatic pressure of several hundred to 1000 bar. Although the same trend is observed in the corresponding system, POPC/30 mol% cholesterol, the observed effects are markedly less pronounced. Whereas the rotational correlation times of the fluorophores decrease in passing the pressure-induced liquid-crystalline to gel phase transition of DPPC, the wobbling diffusion coefficient remains essentially unchanged. The wobbling diffusion constant of the two fluorophores changes markedly upon incorporation of 30 mol% cholesterol, and increases at higher pressures, also in the case of POPC/30 mol% cholesterol. The observed effects are discussed in terms of changes in the rotational characteristics of the fluorophores and the phase-state of the lipid mixture. The results demonstrate the ability of cholesterol to adjust the structural and dynamic properties of membranes composed of different phospholipid components, and to efficiently regulate the motional freedom and hydrophobicity of membranes, so that they can withstand even drastic changes in environmental conditions, such as high external hydrostatic pressure.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1997

Cyclosporine A-induced contraction of isolated rat aortic smooth muscle cells.

The mechanisms by which the immunosuppressive drug cyclosporine A (CsA) induces hypertension and nephrotoxicity are still not fully understood. Although smooth muscle cell (SMC) contraction is probably the mechanism of vasoconstriction, the direct contractive effect of CsA on SMCs has not yet been demonstrated. Thus, it was the purpose of this study to evaluate the direct effects of CsA in cultured SMCs through interactive image analysis. In aortic SMCs, CsA at the concentrations of 0.01, 0.1 and 1 microM, caused a concentration-dependent decrease of the planar cross-sectional area (PCSA) after 30 min and 60 min of treatment. The PCSA decreases were statistically significantly different from control at all concentrations. No cytotoxicity was observed under these conditions. Ten minutes preincubation of SMCs with a monoclonal antibody against endothelin-1 (ET-1) significantly prevented the CsA effects at 1 microM. When the same antibody was heat inactivated or an unspecific antibody (anti-desmin immunoglobulin G) was applied, the CsA-induced contractions were not affected. These data suggest that CsA can cause a direct contractive effect on vascular SMCs. This effect is partly mediated by ET-1.

Animals↗
PubMed1997

Fructose and tagatose protect against oxidative cell injury by iron chelation.

To further investigate the mechanism by which fructose affords protection against oxidative cell injury, cultured rat hepatocytes were exposed to cocaine (300 microM) or nitrofurantoin (400 microM). Both drugs elicited massively increased lactate dehydrogenase release. The addition of the ketohexoses D-fructose (metabolized via glycolysis) or D-tagatose (poor glycolytic substrate) significantly attenuated cocaine- and nitrofurantoin-induced cell injury, although both fructose and tagatose caused a rapid depletion of ATP and compromised the cellular energy charge. Furthermore, fructose, tagatose, and sorbose all inhibited in a concentration-dependent manner (0-16 mM) luminolenhanced chemiluminescence (CL) in cell homogenates, indicating that these compounds inhibit the iron-dependent reactive oxygen species (ROS)-mediated peroxidation of luminol. Indeed, both Fe2+ and Fe3+ further increased cocaine-stimulated CL, which was markedly quenched following addition of the ketohexoses. The iron-independent formation of superoxide anion radicals (acetylated cytochrome c reduction) induced by the prooxidant drugs remained unaffected by fructose or tagatose. The iron-chelator deferoxamine similarly protected against prooxidant-induced cell injury. In contrast, the nonchelating aldohexoses D-glucose and D-galactose did not inhibit luminol CL nor did they protect against oxidative cell injury. These data indicate that ketohexoses can effectively protect against prooxidant-induced cell injury, independent of their glycolytic metabolism, by suppressing the iron-catalyzed formation of ROS.

Adenosine Triphosphate↗
PubMed1997

Insulin resistance with altered secretory kinetics and reduced proinsulin in cystic fibrosis patients.

BACKGROUND: Impaired glucose tolerance and secondary diabetes are frequent in older patients with cystic fibrosis (CF), associated with increased frequency of infections and reduced life expectancy. Studies on the pathophysiology of islet cell secretion in CF are a prerequisite for a scientifically based therapeutic approach. METHODS: Oral glucose tolerance tests were performed in 71 patients (14.2 +/- 0.5 years; mean +/- SE) and 56 control subjects (16.5 +/- 0.9 years). Glucose, insulin, C-peptide, and proinsulin were measured every 30 min. RESULTS: Glucose tolerance in CF patients was classified as normal (NGT, n = 48), impaired (IGT, n = 14), or diabetic (DM, n = 9). Even in CF patients with NGT, blood glucose was significantly elevated at 30, 60, and 90 min of the test. Surprisingly, the secretory responses of insulin and C-peptide were not reduced in CF patients with IGT or DM compared with both healthy controls or CF patients with normal glucose tolerance. However, peak insulin concentration was reached at 90 min in CF-IGT or CF-DM patients compared with 30 min in controls. The ratio of glucose to insulin, an indicator of insulin resistance, increased in CF patients with progression of carbohydrate intolerance. Proinsulin was significantly reduced in all CF patients compared with controls (p < 0.001; Wilcoxon's rank sum test). CONCLUSIONS: In CF patients with impaired glucose tolerance or diabetes, integrated insulin release is not diminished, indicating that insulin resistance is likely to contribute to hyperglycemia in CF patients with IGT or DM. Reduced proinsulin levels in CF patients are compatible either with enhanced conversion of proinsulin to insulin in compensation for reduced beta-cell mass, or enhanced clearance of proinsulin.

Adolescent↗
PubMed1997

Maternity blues in Brazilian women.

In this prospective study, a sample of 86 postpartum women was compared with a sample of 75 women from a random period of 8 consecutive days out of puerperium. Symptoms were evaluated each day using the Blues Questionnaire. Postpartum women and women out of puerperium showed a different distribution of percentile scores on the scale on the third, fourth and fifth days. The postpartum symptom peak occurred on the fifth day. Symptoms more significantly associated with the third, fourth and fifth postpartum days were overemotionalism and oversensitivity. It is concluded that maternity blues in Brazilian women appear to be characterized by maternal mental state alterations occurring on the third, fourth and fifth days postpartum. MB seems to be better defined as an emotional oversensitivity syndrome of cross-cultural dimension than as depression.

Adolescent↗