Biomedical subjects

G Romano

Publications and source records attributed to G Romano.

At least 55 records · Page 3Linked to original sources

PubMed2001

Androstanolone treatment for congenital penile curvature.

OBJECTIVES: To test the etiological hypotheses of congenital penile curvature (CPC) and to infer the possible therapeutic approaches. MATERIALS AND METHODS: Seventy patients affected by CPC were enlisted for the present study: 37 with left curvature, 21 with ventral curvature, 11 with left ventral-lateral curvature, and 1 with right curvature. All patients under the age of 21 years were encouraged to take local medical therapy with alcohol androstanolone gel in a dosage of 0.15 mg/cm(2) of surface area. Group A (17-43 years of age) consisted of patients who refused medical therapy and decided to solve their problem with surgery. They underwent Nesbit's operation and were given a contralateral biopsy of the tunica albuginea at the same time. Cytoplasmic androgen receptors (CARs) were quantified in the tunica albuginea of both cavernous bodies (CBs). Group B consisted of 26 patients aged between 4 and 21 years who were given local medical therapy with androstanolone in alcohol gel. They underwent a maximum of 3 therapy cycles each lasting 2 months with a 1-month suspension between each. Group C consisted of 9 patients (27-53 years of age) who were fathers of 9 group B patients. These adults were also affected by penile curvature and taken into consideration as a control group because we have observed three spontaneous corrections of penile curvature in puberty. RESULTS: CARs research in group A and in 6 group B patients under the age of 20 revealed a 2-5 times reduction on the concave part of the cavernous body compared to the contralateral one. This difference progressively decreased in older patients. In group B, 14 patients aged between 4 and 15 years and 1 aged 17 (53.8%) were treated with a local androstanolone therapy and the result was a regression in the curvature between 30 and 100%. Another 9 patients aged between 17 and 21 years did not show any improvement despite androstanolone treatment. CONCLUSIONS: The results show a 2-5 times reduction in CARs on the hypoplastic cavernous body of young male patients. These differences progressively decreased in older patients. The positive results of the androstanolone therapy in patients under the age of 15 and the negative ones in older patients are certainly related to the quantity of CARs present on the tunica albuginea.

Adolescent↗

PubMed2001

Regulation of Id2 gene expression by the type 1 IGF receptor and the insulin receptor substrate-1.

The Id family of helix-loop-helix proteins is known to be involved in the proliferation and differentiation of several types of cells. The type 1 IGF receptor (IGF-IR) induces either proliferation or differentiation in 32D cells, a murine hemopoietic cell line, depending on the availability of the appropriate substrates for the receptor. We have previously reported that the IGF-IR regulates the expression of the Id2 gene in 32D cells. We now show that the IGF-IR controls the increase in Id2 gene expression through at least three pathways. These three pathways originate from the tyrosine residue at 950, a domain in the C-terminus, and the activation of the insulin receptor substrate-1 (IRS-1) by the receptor. IRS-1 is the preponderant signal, and its effect on Id2 gene expression requires a functional phosphotyrosine binding domain. With wild-type IRS-1, Id2 gene expression is increased, even in those cells that express IGF-I receptors defective in Id2 signaling. Rapamycin, an inhibitor of p70(S6K), a downstream effector of IRS-1 signaling, partially inhibits (but does not completely abrogate) the increase in Id2 gene expression. A mutant IRS-1 with a deletion of the Pleckstrin domain is as effective as wild-type IRS-1 in up-regulating Id2 gene expression. In addition, it seems to increase the stability of p70(S6K). Our results indicate that the IGF-IR regulates Id2 gene expression through different pathways. At least in 32D cells, increased Id2 gene expression seems to correlate more with inhibition of differentiation than with proliferation.

Animals↗

PubMed2001

Associated vascular lesions in patients undergoing coronary artery bypass grafting.

Atherosclerotic involvement of extracoronary arteries in patients undergoing myocardial revascularization can cause severe postoperative complications and increase postoperative mortality. Between January and November 1998, routine preoperative echo-Doppler study of carotid vessels, abdominal aorta and iliac-femoral arteries was performed in all patients undergoing coronary artery bypass grafting (CABG) at our institution, in order to assess the prevalence and the degree of associated vascular lesions. Correlations between echo-Doppler findings, angiographic patterns of coronary lesions and atherosclerotic risk factors were analyzed in all cases. Among 302 patients undergoing CABG, 186 (61.6%) had carotid disease, with a haemodynamically significant stenosis (>70%) of internal carotid in 31 (10.2%). Twenty-three patients had asymptomatic severe carotid disease. A significant correlation between severity of coronary disease and prevalence of severe carotid disease was found (p = 0.02). An abdominal aortic dilatation (diameter > 25 mm) was found in 20 cases (6.6%), with a diameter >35 mm in 7 patients (2.3%), 6 with triple-vessel coronary disease, and 1 with double-vessel disease. Atherosclerotic lesions of iliac-femoro-popliteal axis were found in 165 (54.6%) patients, with a strong correlation to the severity of coronary disease (p = 0.02); lesions were haemodynamically significant (> 70%) in 48 (15.8%) cases. Symptoms of carotid and peripheral vascular disease are no reliable predictors of perioperative risk in patients undergoing CABG. Non-invasive complete arterial investigation should be routinely performed in these patients, in order to plan the most suitable operative approach and to prevent perioperative vascular complications.

Adult↗

PubMed2001

Surgery of rheumatic mitral stenosis: comparison of different techniques.

OBJECTIVE: The breakthrough of percutaneous transvenous mitral commissurotomy (PTMC) has dramatically changed the indications for the surgical treatment of rheumatic mitral stenosis over the last decade. No recent studies comparing long-term results of PTMC, open mitral commissurotomy (OMC) and mitral valve replacement (MVR) with bileaflet prostheses are available in medical literature. METHODS AND RESULTS: Between January 1991 and December 1997, 313 patients with pure and isolated rheumatic stenosis were treated in our department. One hundred and eleven patients underwent PTMC, 82 OMC and 120 MVR. There was no statistical difference (p>0.05) between the mortality rates of the three groups of patients. No cases of hospital mortality were observed in the patients who underwent PTMC and OMC, whereas two patients (1.6%) died within 30 days after MVR. Seven year actuarial survival results are: 95.41+/-2(SE)% (PTMC), 98.05+/-1% (OMC) and 92.82+/-33% (MVR) (p=NS). Freedom from embolism was 98.78+/-1% in PTMC, 98.78+/-1% in OMC and 92.52+/-2% in MVR (p>0.05); freedom from reoperation was 88.43+/-8% in PTMC, 96.35%+/-2% in OMC and 97.72+/-1% in MVR (p>0.05). The mean NYHA class at the end of follow-up was lower in OMC (1.14+/-0.3) versus PTMC (1.39+/-0.6) and MVR (1.41+/-0.71) (p=0.001). CONCLUSIONS: Even though conservative techniques are the first option to consider in treating mitral valve stenosis, valve replacement with bileaflet prostheses no longer represents a limiting factor to survival and quality of life.

Adult↗

PubMed2001

[Prevalence of vascular disease in candidates for myocardial revascularization with aortocoronary bypass: review of the literature and practical implications].

BACKGROUND: Cardiovascular disease remains the main cause of death and morbidity in the industrialized world. Atherosclerosis is a slowly progressive disease; coronary artery disease may be the first presentation of a systemic pathology. The association between coronary artery disease and peripheral vascular disease has often been confirmed by multicenter trials; nevertheless it still remains a subject of debate. METHODS: In order to assess the incidence of coronary artery disease and the degree of associated vascular lesions, between January 1997 and September 1999, in the Department of Cardiothoracic Surgery of the Second University of Naples (Italy), all candidates to coronary artery bypass grafting (CABG) were submitted to routine preoperative echo color Doppler study of the carotid vessels, abdominal aorta and iliac-femoral arteries. The correlation between the echo color Doppler findings, the angiographic patterns of coronary lesions and atherosclerotic risk factors was analyzed in all cases. RESULTS: Among 540 patients undergoing CABG, 418 (77.4%) had carotid disease, with a stenosis > 70% in 62 (11.3%). Forty-nine (79%) patients had asymptomatic severe carotid disease. A significant correlation between the severity of coronary disease and the incidence of severe carotid disease was found (p = 0.02). An abdominal aortic dilation was found in 37 cases (6.7%). Its diameter exceeded 35 mm in 14 patients (2.5%) and in 8 it was associated with triple vessel coronary disease. Atherosclerotic lesions of the iliac-femoro-popliteal axis were found in 394 (72.9%) patients and strongly correlated with the severity of coronary artery disease (p = 0.02); lesions were hemodynamically significant in 91 (16.8%) cases. CONCLUSIONS: Our study emphasizes the association between coronary artery disease and vascular disease. Non-invasive complete arterial investigation should be routinely performed in patients undergoing CABG.

Adult↗

PubMed2001

Intracellular association of a mutant insulin-like growth factor receptor with endogenous receptors.

The type 1 insulin-like growth factor receptor (IGF-IR) is emerging as a powerful survival factor against a variety of apoptotic agents in many cell types. A mutant IGF-IR designated 486/STOP is known to induce apoptosis and inhibit the growth of human tumor cells in mice. We have investigated the mechanism of action of 486/STOP. To study it, we have developed a new retroviral vector in which we have combined a self-inactivating 5'-long terminal repeat with an inducible heat-shock promoter (heat shock protein 70) from Drosophila. Using this technique, we find that the polypeptide encoded by 486/STOP is partially retained within the cell and partially secreted. However, the secreted polypeptide is subsequently taken up by the cells. In both cases, a specific intracellular interaction of 486/STOP with the endogenous IGF-IRs can be demonstrated by coimmunoprecipitation.

Agar↗

PubMed2001

Infective endocarditis of native cardiac valves: 22 years' surgical experience.

BACKGROUND AND AIM OF THE STUDY: Most previous studies on surgery for endocarditis included cases of both prosthetic and native valve endocarditis (NVE), which clearly differ in their course and prognosis. METHODS: Between February 1979 and July 2000, 199 patients underwent surgical treatment for NVE. The native valve was replaced in 185 patients, and repaired in 14. Correlations between previous heart disease and site of NVE, site and etiology, site and embolism, and etiology and extracardiac infection were analyzed. Viability of echocardiography to identify NVE features was compared with surgical inspection. Risk factors for hospital, late mortality and recurrence were assessed by multivariate analysis, including preoperative, operative and postoperative variables. RESULTS: Streptococci were found in 52 cases (26.1%), mostly spreading from splanchnic (n = 10) and cutaneous (n = 9) infections; Staphylococci were found in 43 cases (21.6%), mostly from cutaneous foci (n = 20). Tricuspid valve endocarditis was due to Staphylococcus sp. in all documented cases (11/15; p <0.001), while Streptococcus sp. predominated in the mitral (p = 0.026) position. Echocardiography was reliable in identifying anatomic features of NVE, except for periannular abscess (13 versus 31 found at surgery; p <0.001). Hospital mortality was 6% (n = 12): preoperative NYHA class IV (p = 0.034) and emergency surgery (p = 0.001) were significant predictors of mortality. Average follow up was 57.2+/-4.4 months and was 96.3% complete. There were 27 late deaths (15%). Actuarial survival was 75.7% at 10 years and 60.3% at 20 years. Low social status (p = 0.022), diabetes mellitus (p = 0.003), fever at time of surgery (p = 0.041) and persistent postoperative fever (p = 0.0002) were predictors for late mortality. Endocarditis recurred in 28 patients (15.5%), with 74.1% freedom at 10 years and 68.7% at 20 years. Drug abuse (p = 0.001), mitral endocarditis (p = 0.002), positive blood cultures (p = 0.0003), homograft implantation (p = 0.0012) and persistent postoperative fever (p <0.0001) were significant predictors for recurrence. CONCLUSION: Preoperative conditions of patients with NVE significantly affect early and long-term outcomes. Prognosis is worsened by delayed diagnosis and operation during the active septic process.

Adolescent↗

PubMed2001

Serum anti-p53 autoantibodies in patients with type 1 diabetes.

The presence of antibodies reacting with the p53 tumor suppressor protein has been described in patients with some autoimmune disorders. In this study we looked for serum anti-p53 antibodies in 64 patients with autoimmune type 1 diabetes mellitus within 4 mo of diagnosis. The presence of anti-p53 antibodies was observed in 6/64 (9.4%) subjects with type 1 diabetes, and in 1/44 (2.3%) subjects with other organ-specific autoimmune diseases (18 primary biliary cirrhosis, 10 autoimmune hepatitis, 16 thyroid diseases), but in none of 45 control subjects. No relationship was found between antibodies directed against islet- and non-islet-specific antigens and anti-p53 antibodies. These findings support a possible role for p53 in some autoimmune disorders.

Adolescent↗

PubMed2000

Insulin receptor substrate-1, p70S6K, and cell size in transformation and differentiation of hemopoietic cells.

After an initial burst of cell proliferation, the type 1 insulin-like growth factor receptor (IGF-IR) induces granulocytic differentiation of 32D IGF-IR cells, an interleukin-3-dependent murine hemopoietic cell line devoid of insulin receptor substrate-1 (IRS-1). The combined expression of the IGF-IR and IRS-1 (32D IGF-IR/IRS-1 cells) inhibits IGF-I-mediated differentiation, and causes malignant transformation of 32D cells. Because of the role of IRS-1 in changing the fate of 32D IGF-IR cells from differentiation (and subsequent cell death) to malignant transformation, we have looked for differences in IGF-IR signaling between 32D IGF-IR and 32D IGF-IR/IRS-1 cells. In this report, we have focused on p70(S6K), which is activated by the IRS-1 pathway. We find that the ectopic expression of IRS-1 and the inhibition of differentiation correlated with a sustained activation of p70(S6K) and an increase in cell size. Phosphorylation in vivo of threonine 389 and, to a lesser extent, of threonine 421/serine 424 of p70(S6K) seemed to be a requirement for inhibition of differentiation. A role of IRS-1 and p70(S6K) in the alternative between transformation or differentiation of 32D IGF-IR cells was confirmed by findings that inhibition of p70(S6K) activation or IRS-1 signaling, by rapamycin or okadaic acid, induced differentiation of 32D IGF-IR/IRS-1 cells. We have also found that the expression of myeloperoxidase mRNA (a marker of differentiation, which sharply increases in 32D IGF-IR cells), does not increase in 32D IGF-IR/IRS-1 cells, suggesting that the expression of IRS-1 in 32D IGF-IR cells causes the extinction of the differentiation program initiated by the IGF-IR, while leaving intact its proliferation program.

Animals↗

PubMed2000

Human dbl proto-oncogene in 85 kb of xq26, and determination of the transcription initiation site.

The dbl oncogene is generated by substitution of the 5' portion of its normal counterpart with an unrelated human sequence. To analyze the genomic structure and transcriptional regulation of the dbl proto-oncogene, we have isolated human genomic clones containing the entire human proto-dbl gene, localized in Xq26. Restriction mapping of a 600kb YAC clone (yWXD311) placed proto-dbl about 50kb telomeric to the coagulation Factor IX gene. The genomic DNA fragment containing the 5' end of proto-dbl was subcloned into plasmid vectors and the nucleotide sequences of exon 1, the flanking intronic region and genomic DNA 5' of the first codon were determined. Sequence analysis of 85119bp from the region revealed the genomic structure of proto-dbl. It contains 25 exons coding for a 4.7kb transcript including large 5'- and 3'- (1218bp and 701bp, respectively) untranslated regions (UTRs). RNase protection and primer extension assays on RNA from medullary thyroid carcinoma (TT) cells, which normally express dbl, revealed a transcription start site 1218bp upstream of the ATG of the first exon. A 1.6kb genomic 5' of the translation start sites drives the expression of a CAT-reporter in transient transfections in the TT cell line, though lacking TATA or CAAT boxes.

Base Sequence↗

PubMed2000

Systemic and intratubular effects of cyclosporin-A and tacrolimus on the rat kidney.

Cyclosporin-A and tacrolimus can cause hypertension and renal failure through endothelin receptors. The importance of tubular function was never investigated. The aim of this study was to compare the effects of intratubular injection of cyclosporin-A and tacrolimus with effects observed during systemic infusion. In 20 rats, either cyclosporin-A or tacrolimus was infused, 30 and 1 mg/kg i.v., respectively, in 30 min. Before and after administration, glomerular filtration rate, single nephron filtration rate, proximal and distal absolute reabsorption and percent reabsorption were measured by clearance and micropuncture techniques. In 22 other rats, single nephron filtration rate, absolute reabsorption, percent reabsorption, were measured at the last proximal and early distal tubules before and during intraluminal microinjection of either cyclosporin-A or tacrolimus. During cyclosporin-A and tacrolimus i.v. infusion, glomerular filtration rate fell from 536+/-43 to 448+/-37 microl/min (P<0.026) and from 408+/-33 to 284+/-81 microl/min (P<0. 02), single nephron filtration rate from 26.4+/-2.0 to 20.6+/-1.9 (P<0.002) and from 21.6+/-2.2 to 17.4+/-2.0 nl/min, respectively (P<0.02). The last proximal absolute reabsorption remained unchanged with cyclosporin-A (16.8+/-2.2 vs. 15.1+/-1.7 nl/min, P>0.444), but was slightly reduced by tacrolimus (14.4+/-1.7 vs. 11.3+/-1.7 nl/min, P<0.05). During microinjection, single nephron filtration rate was increased by cyclosporin-A (20+/-1 vs. 63+/-8 nl/min, P<0.0001), and tacrolimus (from 17+/-2 to 49+/-9 nl/min, P<0.0001), and so was reabsorption, independent of the sampling site. Cyclosporin-A and tacrolimus, indeed, raise single nephron filtration rate directly when injected intraluminally. Since this effect occurs in the direction opposite to that recorded during systemic infusion, it must be mediated through different pathways. The i.v. infusion of cyclosporin-A, but not tacrolimus, impairs glomerulo-tubular balance.

Absorption↗

PubMed2000

IGF-I receptor signaling in a prostatic cancer cell line with a PTEN mutation.

LNCaP prostatic cancer cells are characterized by having a PTEN mutation, low levels of type 1 insulin-like growth factor receptor (IGF-IR) and no IRS-1, one of the major substrates of the IGF-IR. The absence of IRS-1, an activator of PI3-kinase, is compensated in these cells by the mutation in PTEN, an inhibitor of PI3-kinase. However, IGF-IR signaling in the absence of IRS-1 can cause cell differentiation and growth arrest. We hypothesized that these three characteristics may not be unrelated, specifically that, together, they may favor the metastatic spread of prostatic cancer cells without decreasing their growth potential. In support of this hypothesis, we report here that: (1) IRS-1 expression increases cell adhesion and decreases cell motility; (2) over-expression of the IGF-IR, in the absence of IRS-1, causes growth arrest and (3) a combination of IGF-IR and IRS-1 restores the transformed phenotype of LNCaP cells. These findings suggest a mechanism by which prostatic cancer cells can achieve metastatic potential without interfering with their growth potential. Oncogene (2000).

Animals↗

PubMed2000

Insulin-like growth factor I receptor signaling in differentiation of neuronal H19-7 cells.

The type I insulin-like growth factor receptor (IGF-IR) is known to send two seemingly contradictory signals inducing either cell proliferation or cell differentiation, depending on cell type and/or conditions. H19-7 cells are rat hippocampal neuronal cells immortalized by a temperature-sensitive SV40 large T antigen that grow at 34 degrees C in epidermal growth factor or serum but differentiate at 39 degrees C when induced by basic fibroblast growth factor. At 39 degrees C, expression of the human IGF-IR in H19-7 cells induces an insulin-like growth factor (IGF) I-dependent differentiation. We have investigated the domains of the IGF-IR required for differentiation of H19-7 cells. The tyrosine 950 residue and serines 1280-1283 in the COOH terminus of the receptor are required for IGF-I-induced differentiation at 39 degrees C, although they are dispensable for IGF-I-mediated growth at 34 degrees C. Both domains have to be mutated to inactivate the differentiating function. The inability of these mutant receptors to induce differentiation correlates with mitogen-activated protein kinase activation. In contrast, inhibitors of phosphatidylinositol 3'-kinase have no effect on IGF-I-mediated differentiation of H19-7 cells, although they do inhibit the mitogenic response.

Adaptor Proteins, Signal Transducing↗

PubMed2000

Mutations in the retinoblastoma-related gene RB2/p130 in lung tumors and suppression of tumor growth in vivo by retrovirus-mediated gene transfer.

The retinoblastoma (Rb) family consists of the tumor suppressor pRb/p105 and related proteins p107 and pRb2/p130. Recent immunohistochemical studies of the retinoblastoma family of proteins in 235 specimens of lung cancer show the tightest inverse association between the histological grading in the most aggressive tumor types and pRb2/p130. This led us to study a panel of human lung cancers for mutations in the RB2/p130 gene. Mutations in the Rb-related gene RB2/p130 were detected in 11 of 14 (78.5%) primary lung tumors by single-strand conformation polymorphism and sequence analysis. A Moloney leukemia virus-based retroviral system was set up, and a comparable viral concentration of 1 x 10(7) infectious units/ml was obtained. Retrovirus-mediated delivery of wild-type RB2/p130 to the lung tumor cell line H23 potently inhibited tumorigenesis in vitro and in vivo, as shown by the dramatic growth arrest observed in a colony assay and the suppression of anchorage-independent growth potential and tumor formation in nude mice. The tumors transduced with the RB2/p130 retrovirus diminished in size after a single injection, and a 12-fold reduction in tumor growth after RB2/p130 transduction compared with the Pac-transduced tumors (92% reduction, P = 0.003) and lacZ-transduced tumors (93% reduction, P < 0.001) was found to be statistically significant. These findings provide the missing confirmation that RB2/p130 is a "bona fide" tumor suppressor gene and strengthen the hypothesis that it may be a candidate for cancer gene therapy for lung cancer.

Adenocarcinoma↗

PubMed2000

Overexpression of protectin (CD59) down-modulates the susceptibility of human melanoma cells to homologous complement.

The clinical efficacy of therapeutic complement (C)-activating monoclonal antibodies (mAb) to melanoma-associated antigens can be impaired by the levels of expression of C-inhibitory molecules on neoplastic cells. Protectin (CD59) is a glycosylphosphatidylinositol (GPI)-anchored cell membrane glycoprotein, acting as terminal regulator of C cascade, which is heterogeneously expressed in melanomas and represents the main restriction factor of C-mediated lysis of melanoma cells. Thus, we investigated whether the overexpression of CD59 could influence the constitutive susceptibility of distinct melanoma cells to homologous C. Infection of CD59-positive Mel 100 and 70-W melanoma cells by a retroviral vector carrying the CD59 cDNA, significantly (P < 0.05) upregulated their constitutive expression of CD59, whereas it did not affect that of additional C-regulatory molecules. Transduced CD59 was entirely GPI-anchored and showed a molecular weight identical to native CD59. Additionally, higher amounts of soluble CD59 were detected in the conditioned media of CD59-transduced melanoma cells compared with parental cells. CD59-transduced melanoma cells, sensitized by the anti-GD3 disialoganglioside mAb R24, were significantly (P < 0.05) less susceptible to homologous C-lysis than were parental cells; this effect was fully reverted by the masking of CD59 with F(ab')(2) fragments of the anti-CD59 mAb YTH53.1. These results provide conclusive evidence demonstrating that absolute levels of CD59 expression regulate the susceptibility to homologous C of specific melanoma cells, and suggest an additional explanation for the poor clinical results obtained with C-activating mAb in the clinical setting.

CD59 Antigens↗

PubMed2000

The effect of colchicine on proximal tubular reabsorption.

Aquaporins, expressed in the brush border membrane (BB) could play a pivotal role in glomerulo-tubular balance (GTB) by effecting adaptive changes of water permeability to the variations in the load of filtered solutes. Since aquaporin expression is modulated by microtubule-dependent trafficking between endoplasmic reticulum and cell membranes, we used the microtubule poison colchicine to assess the importance of aquaporins in mediating GTB. The effects of colchicine 1.6x10(-4)m on proximal tubule volume reabsorption was tested on 48 nephrons of ten rats by micropuncture techniques. Thirty proximal tubules were sampled from the last proximal convolution before, and recollected during and again after the microinjection (MIJ), into the early proximal convolution or Bowman's space, of colchicine added to a Ringer solution. We studied 18 proximal tubules in the same way before, during and after the microperfusion (MP) of colchicine added to an ultrafiltrate of plasma into the peritubular capillaries. During MIJ, SNGFR did not change significantly from baseline (17.7+/-1.3 vs 20.9+/-1.8 nl min(-1), P>0.12). Post-control values were superimposable upon their paired pre-MIJ controls, when available (15.8+/-1.3 vs 13.5+/-1.5 nl min(-1), P>0.25). The measurements of percentage reabsorption (49+/-5 during baseline, 45+/-7 during MIJ, and 55+/-5 in post-control, P>0.6) and absolute reabsorption (8.1+/-0.7, 11.1+/-2. 2, and 7.9+/-1.3 nl min(-1), respectively, P>0.18) were also unchanged. The three average measurements obtained in control conditions, during MP and again in post-MP control were not significantly different for SNGFR (19.8+/-3.0, 20.0+/-4.7, and 20. 2+/-3.5 nl min(-1), P>0.48), percentage (55+/-3, 59+/-5, and 47+/-3%, P>0.35) and absolute reabsorptions (12.5+/-2.2, 12.4+/-4.6, and 9. 4+/-1.0 nl min(-1), respectively, P>0.42). MIJ and MP of vehicles were devoid of any measurable effect. Colchicine does not acutely affect volume reabsorption in the proximal tubule. Aquaporin trafficking, if any, is not involved in mediating glomerulotubular balance in the proximal tubule, although aquaporin expression and function could still be important, although regulated by mechanisms different from microtubule-dependent shuttling between endoplasmic reticulum and BB.

Absorption↗

PubMed2000

Dual effect of secretin on nephron filtration and proximal reabsorption depending on the route of administration.

Secretin is a vasoactive peptide capable of acting on transmembrane volume fluxes. We measured nephron filtration (SNGFR) and resorption during secretin microinjection (MIJ) into the tubular lumen or microperfusion (MP) into peritubular capillaries. In 24 rat nephrons, SNGFR, measured by collections from the distal tubule, rose from 25+/- 4 to 61+/-8 nl/min during MIJ of saline containing secretin 10(-9) M into the last convolution of the proximal tubule (LP). Percent and absolute resorptions rose from 70 to 90% and from 20+/-4 to 56+/-8 nl/min, respectively. During MIJ of secretin, 3 x 10(-)(9) M into the first convolution of the proximal tubule, SNGFR, measured at LP, rose from 32+/-4 to 61+/-8 nl/min, percent and absolute reabsorptions from 52+/-4 to 78+/-3% and from 16+/-2 to 50+/-7 nl/min, respectively (n = 30). During MP of secretin, 1.5x10(-9) M, SNGFR fell from 39+/-6 to 15+/-4, resorption from 19+/-4 to 9+/-2 nl/min, while percent resorption rose from 43+/-6 to 59+/-5% (n = 15). While all MIJ and MP changes were significant (P<0.001), paired pre- versus post-MIJ and MP values were not. Secretin is a powerful vasoconstrictor when perfused into peritubular capillary blood, unlike systemic and intra-arterial injections. When injected into the tubular lumen, it up-regulates SNGFR and increases reabsorption directly.

Animals↗

PubMed2000

Regional differences in signalling transduction pathways among smooth muscle cells from rabbit colon.

Smooth muscle cells (SMC) from the circular muscle layer of rabbit colon, taken from the proximal and distal regions that are known to have different physiological and motor activities, were used to highlight distinct regional intrinsic myogenic properties and to investigate the correlations between receptor and signalling transduction pathways. Contractile agonists were shown to be more potent on proximal than on distal SMC in inducing contraction and intracellular Ca(2+) increase. Concentration-response curves of agonists-induced Ca(2+) increase were constantly shifted to the right, though remaining parallel, with respect to contraction curves, independently of the region analysed. Using agents activating different steps of cAMP-or cGMP-mediated intracellular cascades, main regional differences were revealed as far as relaxation was concerned. Relaxation of proximal SMC was found to be essentially cGMP mediated, while that of distal SMC was cAMP mediated. In conclusion, the motor patterns of the two regions appear to be influenced by distinct regional biochemical characteristics that are intrinsic to colonic SMC.

Adrenergic beta-Agonists↗