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R Melchior

Publications and source records attributed to R Melchior.

11 recordsLinked to original sources
PubMed2001

Characteristics associated with the dropout of hypertensive patients followed up in an outpatient referral clinic.

OBJECTIVE: To determine the characteristics associated with the dropout of patients followed up in a Brazilian out patient clinic specializing in hypertension. METHODS: Planned prospective cohort study of patients who were prescribed an antihypertensive treatment after an extensive initial evaluation. The following parameters were analyzed: sex, age, educational level, duration of disease, pressure level used for classifying the patient, previous treatment, physical activity, smoking, alcohol consumption, familial history of hypertension, and lesion in a target organ. RESULTS: We studied 945 hypertensive patients, 533 (56%) of whom dropped out of the follow-up. The mean age was 52.3+/-12.9 years. The highest probabilities of dropout of the follow-up were associated with current smoking, relative risk of 1.46 (1.04-2.06); educational level equal to or below 5 years of schooling, relative risk of 1.52 (1.11-2.08); and hypertension duration below 5 years, relative risk of 1.78 (1.28-2.48). Age increase was associated with a higher probability of follow-up with a relative risk of 0.98 (0.97-0.99). CONCLUSION: We identified a group at risk for dropping out the follow-up, which comprised patients with a lower educational level, a recent diagnosis of hypertension, and who were smokers. We think that measures assuring adherence to treatment should be directed to this group of patients.

Age Factors↗
PubMed2000

Absence of antihyperglycemic effect of jambolan in experimental and clinical models.

The use of alternative therapies to treat diabetes, including teas prepared with different vegetables, is widespread in Brazil. In Porto Alegre, a southern city of Brazil, the tea prepared from leaves of Syzygium cumini (L.) Skeels or S. jambos (L.) Alst has been report to be used frequently by diabetic patients. We investigated the postulated antihyperglycemic effect of the S. cumini (L.) Skeels in three experiments. In the first, a randomized, parallel, placebo controlled trial, tea prepared from leaves of S. cumini did not present any antihyperglycernic effect in 30 non-diabetic young volunteers submitted to a glucose blood tolerance test. In the animal experiments, we tested the effect of increasing doses of the crude extract prepared from leaves of S. cumini administrated for 2 weeks, on the post-prandial blood glucose level of normal rats and rats with streptozotocin-induced diabetes mellitus. The treatment did not produce any antihyperglycernic effect in both models. These results do not rule out hypoglycemic effects in patients with type 2 diabetes mellitus, but strongly suggest that, for a while, the jambolan can not be recommended as an antihyperglycemic treatment.

Adolescent↗
PubMed1998

Alpha2-macroglobulin does not function as a C3 homologue in the plasma hemolytic system of the American horseshoe crab, Limulus.

A major problem of comparative immunology is the characterization of the internal defense systems that lyse foreign cells, such as bacteria and other microbial pathogens that have gained entry into the body. The plasma cytolytic system of the American horseshoe crab, Limulus polyphemus, is sensitive to treatment with methylamine, which inactivates the abundant plasma defense protein alpha2-macroglobulin. This has been interpreted to mean that alpha2-macroglobulin plays an important role in hemolysis, analogous to the role of complement component C3 of the mammalian complement system (Enghild et al., 1990). Sensitivity to methylamine has been suggested to reflect an evolutionary homology with the plasma cytolytic system of mammals, in which the complement system is inactivated by the reaction of methylamine with complement components C3 and C4. C3, C4 and alpha2-macroglobulin contain an internal thiol ester bond linking cysteinyl and glutamic acid residues and methylamine inactivates all three proteins by reaction with the thiol-esterified glutamic acid. However, we have recently shown that the principal effector of hemolysis in Limulus is the plasma lectin, limulin (Armstrong et al., 1996). In this article we show that native, unreacted alpha2-macroglobulin is not involved directly in hemolysis but instead that methylamine-reacted alpha2-macroglobulin inhibits the hemolytic activity of limulin. Thus the thiol ester proteins alpha2-macroglobulin and C3 operate very differently in the hemolytic systems of Limulus and mammals and are not functionally homologous. Limulus alpha2-macroglobulin functions indirectly in hemolysis: its inactivation yields an inhibitory molecule for limulin-mediated hemolysis.

Animals↗
PubMed1995

Alpha 2-macroglobulin-mediated clearance of proteases from the plasma of the American horseshoe crab, Limulus polyphemus.

Because proteases free in the body are damaging to the tissues, animals have evolved various agents for their inactivation and clearance. Mammals, for instance, have a diverse array of active site protease inhibitors in the plasma. In addition, mammals have alpha 2-macroglobulin (alpha 2M), which binds active proteases, and the alpha 2M-protease complex is then cleared from the plasma by a receptor-mediated endocytotic process. alpha 2M is also present in the plasma of many invertebrates, and in the American horseshoe crab, Limulus polyphemus, it is the only protease inhibitor in the plasma. To search for a clearance process for proteases in Limulus, fluorescein isothiocyanate (FITC)-labeled proteins were injected into the blood, and the fluorescence in the plasma and associated with the blood cells was determined. FITC-labeled trypsin was cleared with an initial mixing period (0-10 min) and a rapid clearance period (10-30 min), followed by the reappearance of FITC in the plasma (45-90 min). Before and during the clearance process, the labeled trypsin was associated with a complex having a molecular mass identical to that of Limulus alpha 2M, and that was precipitated by antibodies directed against Limulus alpha 2M. The fluoresceinated material that reappeared in the plasma after 45 min was of low molecular mass (< 10 kDa) and thus appears to have experienced degradation. The clearance of trypsin requires its protease activity, since phenylmethylsulfonyl fluoride-inactivated, FITC-labeled trypsin was cleared only very slowly if at all (t1/2 > 180 min). FITC-labeled, trypsin-reacted Limulus alpha 2M was cleared rapidly from the plasma of Limulus, whereas FITC-labeled, native Limulus alpha 2M persisted undiminished in excess of 400 min. The blood cells of Limulus bound FITC-labeled trypsin-reacted Limulus alpha 2M, and the peak of recovery from the blood cells coincided with the minimum concentration of FITC-labeled protein in the plasma, suggesting that the blood cells participate in the clearance of alpha 2M-protease complex from the plasma. Thus, we have demonstrated the existence of a clearance pathway in Limulus that operates selectively on enzymatically active proteases and have shown that Limulus alpha 2M is the probable agent for protease clearance. This is the first documentation of a protease clearance pathway in invertebrates and represents the first identified physicological function for alpha 2M in invertebrates.

Animals↗
PubMed1993

Tumor necrosis factor alpha (TNF alpha) and transforming growth factor beta 1 (TGF beta 1) stimulate fibronectin synthesis and the transdifferentiation of fat-storing cells in the rat liver into myofibroblasts.

Transforming growth factor-beta (TGF beta 1) and tumor necrosis factor alpha (TNF alpha) stimulate the transdifferentiation of fat-storing cells (FSC) in the rat liver into highly active and "synthetic" myofibroblast-like cells (MFBIC). This activation has been documented by differential-interference contrast and light microscopy using morphologic criteria (a reduction in the number and size of fat droplets, cell flattening and the development of long cytoplasmic extensions), by the loss of retinyl-palmitate (measured by HPLC) and by the enhanced expression of iso-alpha smooth muscle actin (demonstrated by immunofluorescence microscopy). Furthermore, while cell growth measured by the cell count and DNA content is slightly inhibited by TGF beta 1 (0.81 of the control), the combination of TGF beta 1 with TNF alpha stimulates cell proliferation to 1.44 times of the control. In addition the combination of TGF beta and TNF alpha potentiated the stimulatory effect on fibronectin synthesis (TGF beta alone: 1.4 times control; TNF alpha alone: 2.2 times control; TGF beta plus TNF alpha: 4.7 times control). The total protein synthesis was not altered by TGF beta or TNF alpha. In summary the results obtained identify TGF beta and TNF alpha as mediators stimulating key events in liver fibrogenesis (i.e. FSC proliferation, FSC transdifferentiation into MFBIC, and fibronectin synthesis).

Adipose Tissue↗
PubMed1993

The response of rat liver perisinusoidal lipocytes to polypeptide growth regulator changes with their transdifferentiation into myofibroblast-like cells in culture.

During culture on uncoated plastic wells rat liver perisinusoidal lipocytes change their differentiated phenotype (transdifferentiate) within 1-2 weeks and obtain a myofibroblast-like phenotype (myofibroblast-like cells). This transdifferentiation was documented by morphologic (loss of fat droplets, flat cell shape, cytoplasmic extensions, expression of iso-alpha smooth muscle actin) and biochemical criteria (loss of retinyl-palmitate, enhanced matrix synthesis). Whereas transforming growth factor alpha (TGF alpha) stimulated and transforming growth factor beta (TGF beta 1) inhibited the proliferation of perisinusoidal lipocytes (early culture) these cytokines did not effect the growth of the myofibroblast-like cells. Opposite effects were obtained with platelet-derived growth factor (PDGF) which stimulated the growth of myofibroblast-like cells only. Insulin-like growth factor (IGF1) was mitogenic in both perisinusoidal lipocytes and myofibroblast-like cells, respectively. Furthermore, whereas the expression of the mRNAs of decorin and biglycan was stimulated by TGF beta 1 in perisinusoidal lipocytes, the synthesis of these mRNAs was stimulated in myofibroblast-like cells predominantly by TGF alpha. Similar effects of TGF alpha and TGF beta 1 have been observed on the glycosaminoglycan-([35S]sulfate incorporation) and proteoglycan level ([3H]leucin incorporation into decorin and biglycan). Neither IGF1 and PDGF stimulated glycosaminoglycan synthesis in perisinusoidal lipocytes or in myofibroblast-like cells. The results demonstrate that the effects of the polypeptide growth regulators TGF alpha, TGF beta 1 and PDGF depend on the cell phenotype (stage of cell activation/transdifferentiation) and may be completely different in perisinusoidal lipocytes and its transformed counterpart the myofibroblast-like cells.

Adipose Tissue↗
PubMed1992

Activation of rat liver perisinusoidal lipocytes by transforming growth factors derived from myofibroblastlike cells. A potential mechanism of self perpetuation in liver fibrogenesis.

Rat liver perisinusoidal lipocytes (PL) cultured on uncoated plastic transform spontaneously within 6-10 d to myofibroblastlike cells (MFBlC). Parallel to the transformation the TGF alpha- and TGF beta 1-mRNA expression increased and was highest in MFBlC. Competitive radioligand binding assays demonstrated that in contrast to untransformed PL the MFBlC synthesize and secrete transforming growth factor (TGF)-alpha (15 fmol/cell per 24 h) and predominantly the latent form of TGF beta 1 (0.2 fmol/cell per 24 h). Medium conditioned by MFBlC (MFBcM) significantly stimulated PL proliferation with little effect on PL proteoglycan synthesis. By transient acidification of the MFBcM, known to activate the latent form of TGF beta 1, the stimulatory effect on PL proteoglycan synthesis was enhanced and furthermore PL transformation (measured by expression of iso-alpha smooth muscle actin and loss of retinylpalmitate) was accelerated. Preincubation of this medium with neutralizing antibodies to TGF beta resulted in (a) the growth inhibitory effect was converted to a growth stimulation and (b) the stimulatory effect on proteoglycan synthesis was abolished. In summary our data indicate that progressive activation of PL on plastic (transformation to MFBlC) leads to an enhanced expression of the TGF alpha- and TGF beta 1-mRNAs and secretion of the corresponding proteins. Medium conditioned by MFBIC stimulates proliferation, transformation, and PG synthesis of untransformed PL. These mechanisms are suggested to be relevant in self perpetuation of liver fibrogenesis.

Adipose Tissue↗
PubMed1989

Transforming growth factors (TGF alpha and TGF beta 1) stimulate chondroitin sulfate and hyaluronate synthesis in cultured rat liver fat storing cells.

The synthesis of total sulfated glycosaminoglycans (GAG) was stimulated by transforming growth factors (TGF alpha 1.4-fold at 5 ng/ml, and TGF beta 1 2.05-fold at 2.5 ng/ml) in primary cultures of rat liver fat storing cells (FSC). The combination of both TGFs resulted in an additively stimulated synthesis of total sulfated GAG (more than 3-fold), chondroitin sulfate (more than 15-fold) and hyaluronate (3.8-fold), respectively, whereas the formation of dermatan sulfate was unchanged and that of heparan sulfate was slightly reduced. In summary, TGFs were identified as important mediators of stimulated GAG synthesis in those cells of the liver (FSC), which are the primary site of matrix glycoconjugate production.

Animals↗
PubMed1989

The role of thrombocytes in liver fibrogenesis: effects of platelet lysate and thrombocyte-derived growth factors on the mitogenic activity and glycosaminoglycan synthesis of cultured rat liver fat storing cells.

A central problem in the study of the pathogenesis of liver fibrosis (fibrogenesis) is the identification of the cellular sources of the extracellular matrix and the dissection of the molecular mediators stimulating connective tissue synthesis in certain hepatic target cells. In the present study the role of platelets and of some platelet-derived polypeptide growth factors in the proliferation and proteoglycan synthesis of rat liver fat storing cells in culture (the principle connective tissue-producing cell type in liver) was determined. Fat storing cell proliferation was determined by measurement of the DNA-content, and [3H]thymidine- and bromodeoxyuridine-incorporation. Glycosaminoglycan synthesis was determined by the measurement of [35S]sulphate incorporation. Human platelet lysate (0.3 to 2.6 g protein per litre medium) stimulated, in a dose-dependent manner, both the proliferation and glycosaminoglycan synthesis of rat liver fat storing cells kept as a primary culture in Dulbecco's modification of Eagle's medium in the absence of foetal calf serum. More than 70% of the newly synthesized glycosaminoglycans were found in the medium. Among the various thrombocyte-derived polypeptides tested as candidate mediators of the platelet-derived fibrogenic activity, platelet derived growth factor was not effective in enhancing glycosaminoglycan synthesis, and it stimulated the proliferation of fat storing cells only about 2 fold. On the other hand, epidermal growth factor proved to be a stimulus of both processes. Transforming growth factor beta (greater than 10 pmol/l) inhibited foetal calf serum (Dulbecco's modification of Eagle's medium with a fraction of foetal calf serum of 0.1) and epidermal growth factor stimulated proliferation but enhanced the synthesis of sulphated glycosaminoglycans about 2-fold. These results suggest the possible role of transforming growth factor beta as a negative modulator for fat storing cells proliferation but a positive modulator for fat storing cell transformation and extracellular glycosaminoglycan matrix synthesis. Furthermore, our results indicate a cooperation between different hepatic and extrahepatic cell types by paracrine stimulation of fat storing cells. Transforming growth factor beta in combination with epidermal growth factor appear to be candidate mediators of the platelet-derived fibrogenic activity, which stimulates fat storing cells in culture, and might also be effective in vivo during hepatic repair processes following liver injury.

Animals↗