Biomedical subjects

M Parisi

Publications and source records attributed to M Parisi.

At least 19 recordsLinked to original sources

PubMed2006

Primary intramedullary primitive neuroectodermal tumor (PNET)--case report and review of the literature.

Spinal primitive neuroectodermal tumors (PNET) are very rare tumors, and intramedullary localization is even less common. Indeed, amongst the 23 cases of the spinal PNET described in the literature, only eight cases had an intramedullary localization. Following the WHO 2000 classification, PNETs have been considered embryonal tumors composed of undifferentiated neuroepithelial cells with a capacity of differentiation into different cellular lines, such as astrocytic, ependymal, melanotic and muscular. They have been considered to arise from a neoplastic transformation of primitive neuroepithelial cells, thereby making their presence possible in any part of the central nervous system. The optimal treatment for these malignant tumors is not yet clear, although, over the years, radiotherapy has been considered the best treatment for spinal PNETs. The described case is that of a 38-year-old man with a primary intra-extramedullary PNET, treated by laminectomy, open biopsy and chemotherapy. The patient, 18 months after the onset of his symptomatology, died without cerebral tumor involvement.

Adolescent↗

PubMed2005

Asthma in women with endometriosis.

INTRODUCTION: This study aimed to investigate asthma prevalence and severity in women with and without endometriosis. METHODS: Before laparoscopy, asthma prevalence was evaluated in 879 women of reproductive age, undergoing surgery because of benign gynaecological conditions. Diagnosis of bronchial asthma was based on the American Thoracic Society criteria; asthma severity was classified in four categories according to the 2002 Global Initiative for Asthma guidelines. Asthmatic patients completed the Living with Asthma Questionnaire (LWAQ). Endometriosis was confirmed histologically and classified according to the revised American Fertility Society criteria. RESULTS: There were no significant differences in age, smoking status, and other demographic and health characteristics between patients with endometriosis (n = 467) and controls (n = 412). Asthma prevalence was similar in women with (23/467, 4.9%; 95% CI, 3.1-7.3) and without (22/412, 5.3%; 95% CI, 3.4-8.0; P = 0.781) endometriosis. Asthma severity was similar in women with and without endometriosis, with 12 (52.2%) women with endometriosis and 13 (59.1%) controls being in the intermittent (mildest) degree of severity. No significant difference was observed between women with and without endometriosis in the LWAQ total score. CONCLUSIONS: Women with endometriosis do not have an increased risk of having asthma.

Adult↗

PubMed2005

Electrical parameters and water permeability properties of monolayers formed by T84 cells cultured on permeable supports.

T84 is an established cell line expressing an enterocyte phenotype whose permeability properties have been widely explored. Osmotic permeability (POSM), hydraulic permeability (PHYDR) and transport-associated net water fluxes (JW-transp), as well as short-circuit current (ISC), transepithelial resistance (RT), and potential difference (deltaVT) were measured in T84 monolayers with the following results: POSM 1.3 +/- 0.1 cm.s-1 x 10-3; PHYDR 0.27 +/- 0.02 cm.s-1; RT 2426 +/- 109 omega.cm2, and deltaVT 1.31 +/- 0.38 mV. The effect of 50 microM 5,6-dichloro-1-ethyl-1,3-dihydro-2H-benzimidazol-2-one (DCEBIO), a "net Cl- secretory agent", on T84 cells was also studied. We confirm the reported important increase in ISC induced by DCEBIO which was associated here with a modest secretory deltaJW-transp. The present results were compared with those reported using the same experimental approach applied to established cell lines originating from intestinal and renal epithelial cells (Caco-2, LLC-PK1 and RCCD-1). No clear association between PHYDR and RT could be demonstrated and high PHYDR values were observed in an electrically tight epithelium, supporting the view that a "water leaky" barrier is not necessarily an "electrically leaky" one. Furthermore, the modest secretory deltaJW-transp was not consistent with previous results obtained with RCCD-1 cells stimulated with vasopressin (absorptive fluxes) or with T84 cells secreting water under the action of Escherichia coli heat stable enterotoxin. We conclude that, while the presence of aquaporins is necessary to dissipate an external osmotic gradient, coupling between water and ion transport cannot be explained by a simple and common underlying mechanism.

Cell Line↗

PubMed2005

Asymmetry in the osmotic response of a rat cortical collecting duct cell line: role of aquaporin-2.

Transition from antidiuresis to diuresis exposes cortical collecting duct cells (CCD) to asymmetrical changes in environment osmolality, inducing an osmotic stress, which activates numerous membrane-associated events. The aim of the present work was to investigate, either in the presence or not of AQP2, the transepithelial osmotic water permeability (P(osm)) following cell exposure to asymmetrical hyper- or hypotonic gradients. For this purpose, transepithelial net volume fluxes were recorded every minute in two CCD cell lines: one not expressing AQPs (WT-RCCD(1)) and another stably transfected with AQP2 (AQP2-RCCD(1)). Our results demonstrated that the rate of osmosis produced by a given hypotonic shock depends on the gradient direction (osmotic rectification) only in the presence of apical AQP2. In contrast, hypertonic shocks elicit P(osm) rectification independently of AQP2 expression, and this phenomenon may be linked to modulation of basolateral membrane permeability. No asymmetry in transepithelial resistance was observed under hypo- or hypertonicity, indicating that rectification cannot be attributed to a shunt through the tight junction path. We conclude that osmotic rectification may be explained in terms of dynamical changes in membrane permeability probably due to activation/incorporation of AQPs or transporters to the plasma membrane via some mechanism triggered by osmolality.

Animals↗

PubMed2002

Differential role of Na+/H+ exchange isoforms NHE-1 and NHE-2 in a rat cortical collecting duct cell line.

The Na+/H+ exchanger (NHE) constitutes a gene family containing several isoforms that display different membrane localization and are involved in specialized functions. Although basolateral NHE-1 activity was described in the cortical collecting duct (CCD), the localization and function of other NHE isoforms is not yet clear, This study examines the expression, localization, and regulation of NHE isoforms in a rat cortical collecting duct cell line (RCCD1) that has previously been shown to be a good model of CCD cells. Present studies demonstrate the presence of NHE-1 and NHE-2 isoforms, but not NHE-3 and NHE-4, in RCCD1 cells. Cell monolayers, grown on permeable filters, were placed on special holders allowing independent access to apical and basolateral compartments. Intracellular pH (pHi) regulation was spectrofluorometrically studied in basal conditions and after stimulation by NH4Cl acid load or by a hyperosmotic shock. In order to differentiate the roles of NHE-1 and NHE-2, we have used HOE-694, an inhibitor more selective for NHE-1 than for NHE-2. The results obtained strongly suggest that NHE-1 and NHE-2 are expressed in the basolateral membrane but that they have different roles: NHE-1 is responsible for pHi recovery after an acid load and NHE-2 is mainly involved in steady-state pHi and cell volume regulation.

Animals↗

PubMed2002

Protoplasmic pH modifies water and solute transfer in beta vulgaris root vacuoles.

Volume changes were studied in Beta vulgaris storage root vacuoles, using video microscopy, when exposed to hypotonic conditions. The osmotic gradient was either step-applied or progressively imposed in perfusion experiments. Preincubation at low pH (6.6) or with HgCl2 strongly reduced the vacuoles' water permeability, measured in step experiments. Furthermore, the volumetric response depended on the rate with which the aniso-osmotic condition was established. In perfusion experiments a "plateau value" (osmotic equilibrium or steady-state volume value) was observed, which was significantly lower than the theoretically expected one. Furthermore, if vacuoles were preincubated in presence of HgCl2 or at low pH and then the hypo-osmotic challenge was applied in perfusion experiments, a still lower "plateau value" was observed. This reduction was concentration-dependent and completely reversible. In these conditions, when HgCl2 concentration was 300 mM or medium pH was 6.6, the volume change was abolished. In other experiments, when urea iso-osmotically replaced mannitol, a reversible, pH-dependent volumetric response was observed. These results can be interpreted accepting that 1) mercury-sensitive water channels, present in the studied structure, were blocked by low pH during the hypo-osmotic challenge; 2) modification of water permeability prevents excessive swelling during the osmotic shock; 3) the effectiveness of this last mechanism depended on the osmotic challenge rate; and 4) additionally, urea reflection coefficients were also modified by reduced medium pH.

Beta vulgaris↗

PubMed2002

Digital cineradiographic swallow study: our experience.

PURPOSE: Swallowing disorders can be secondary to different types of diseases in which, at least initially, patients succeed in establishing voluntary or involuntary compensatory mechanisms that enable them to maintain a sufficient nutritional state. When the compensatory mechanisms become insufficient massive food aspiration into the airways can occur and suffocation may prove to be the main pathology. It has been calculated that in the USA about 8,000-10,000 people die each year due to suffocation. The dynamic radiological examination of swallowing is considered important not only for diagnosis, but also for planning a rehabilitation therapy and type of nutrition for the patient and for verifying the results of the therapy. The aim of this study is to analyse the results of our experience in the use of the digital cineradiography system to evaluate patients with normal and pathological swallowing. MATERIALS AND METHODS: We reviewed the digital cineradiography of 220 patients that at no time had undergone surgery and presented no organic pharyngeal or oesophageal disease (excluding hiatus hernia). All the exams followed a standard protocol that included the dynamic evaluation of the larynx, soft palate, pharynx, and gastro-oesophageal junction with a cineradiographic sequence of 12 frames/second with a 512x1024 matrix. There was also an archive of the film in a post-processing console. The patients received single photograms (printed on laserfilm), videotape recordings or CD-ROM of the dynamic exam. RESULTS: 137 (62%) of the patients did not present swallowing alterations although only 7 patients had a negative examination. In 35 cases hiatus hernia was appreciable while in 69 cases the hernia was associated with gastro-oesophageal reflux. In 23 cases aspecific functional disorders of the oesophagus were demonstrated and in 3 cases achalasia. The remaining 83 patients (38%) (37 males and 46 females, average age 57.02 yrs) presented alterations of the oral and/or pharyngeal stages of swallowing: reduction in soft-palate motility (2 cases), unilateral paralysis of the vocal chords (1 case), incontinence of the bolus during the oral stage (8 cases), lingual movement anomalies (4 cases), subepiglottic penetration (62 cases), asymmetric epiglottic tilt, aspiration of the contrast medium in the airway (17 cases), reduction of laryngeal and hyoid bone movement (9 cases), bolus retained in the valleculae and pyriform sinus (13 cases), cricopharyngeal spasm (6 cases), pharyngeal paralysis (1 case); hiatus hernia was also evident in 20 cases and gastro-oesophageal reflux was associated in 13 of them. Overall, 36% of the cases presented an isolated form while 64% of the cases presented a complex dysfunction with several simultaneous alterations. DISCUSSION AND CONCLUSIONS: The videofluorographic swallow study is an important step in the diagnostic evaluation of a dysphagic patient not only as regards the analysis of the main alteration and its capacity to confirm the presence or absence of contrast medium aspiration in the airway, but also because it provides important information on rehabilitation and nutritional orientation (oral/no oral), as well as on the results of the therapy. The recent diffusion of the digital X-ray equipment has made possible its use for the study of the organic and functional diseases of the upper alimentary tract. Currently a standard protocol for the study of swallowing with digital fluorography is not available. The technique we applied, already verified in a significant number of dysphagic patients, has allowed us to distinguish patients with normal swallowing from those with disorders of the oral and pharyngeal stage, and thus to identify disturbance and establish an appropriate rehabilitation treatment.

Adolescent↗

PubMed2001

Association of germline mutation in the PTEN tumour suppressor gene and Proteus and Proteus-like syndromes.

The molecular aetiology of Proteus syndrome (PS) remains elusive. Germline mutations in PTEN cause Cowden syndrome and Bannayan-Riley-Ruvalcaba syndrome, which are hereditary hamartoma syndromes. Some features-eg, macrocephaly, lipomatosis, and vascular malformations-can be seen in all three syndromes. We examined PTEN in patients with PS and undefined Proteus-like syndromes (PS-like) and identified de-novo germline mutations in two of nine patients with PS and three of five patients with PS-like. Germline PTEN mutation analysis should be done in individuals with PS and PS-like because of its association with increased risk of cancer development and potential of germline-mutation transmission.

Genes, Tumor Suppressor↗

PubMed2001

Vasopressin regulates water flow in a rat cortical collecting duct cell line not containing known aquaporins.

Transepithelial water movements and arginine-vasopressin (AVP)-associated ones were studied in a renal cell line established from a rat cortical collecting duct (RCCD(1)). Transepithelial net water fluxes (J(w)) were recorded every minute in RCCD(1) monolayers cultured on permeable supports. Spontaneous net water secretion was observed, which was inhibited by serosal bumetanide (10(-5) m), apical glibenclamide (10(-4) m) and apical BaCl(2) (5 x 10(-3) m). RT-PCR, RNAse protection and/or immunoblotting experiments demonstrated that known renal aquaporins (AQP1, AQP2, AQP3, AQP4, AQP6 and AQP7) were not expressed in RCCD(1) cells. AVP stimulates cAMP production and sodium reabsorption in RCCD(1) cells. We have now observed that AVP significantly reduces the spontaneous water secretory flux. The amiloride-sensitive AVP-induced increase in short-circuit current (I(sc)) was paralleled by a simultaneous modification of the observed J(w): both responses had similar time courses and half-times (about 4 min). On the other hand, AVP did not modify the osmotically driven J(w) induced by serosal hypertonicity. We can conclude that: (i) transepithelial J(w) occurs in RCCD(1) cells in the absence of known renal aquaporins; (ii) the "water secretory component" observed could be linked to Cl- and K = secretion; (iii) the natriferic response to AVP, preserved in RCCD(1) cells, was associated with a change in net water flux, which was even observed in absence of AQP2, AQP3 or AQP4 and (iv) the hydro-osmotic response to AVP was completely lost.

Animals↗

PubMed2001

Spontaneous water secretion in T84 cells: effects of STa enterotoxin, bumetanide, VIP, forskolin, and A-23187.

The regulated Cl(-) secretory apparatus of T84 cells responds to several pharmacological agents via different second messengers (Ca(2+), cAMP, cGMP). However, information about water movements in T84 cells has not been available. In the absence of osmotic or chemical gradient, we observed a net secretory transepithelial volume flux (J(w) = -0.16 +/- 0.02 microl.min(-1).cm(-2)) in parallel with moderate short-circuit current values (I(sc) = 1.55 +/- 0.23 microA/cm(2)). The secretory J(w) reversibly reverted to an absorptive value when A-23187 was added to the serosal bath. Vasoactive intestinal polypeptide increased I(sc), but, unexpectedly, J(w) was not affected. Bumetanide, an inhibitor of basolateral Na(+)-K(+)-2Cl(-) cotransporter, completely blocked secretory J(w) with no change in I(sc). Conversely, serosal forskolin increased I(sc), but J(w) switched from secretory to absorptive values. Escherichia coli heat-stable enterotoxin increased secretory J(w) and I(sc). No difference between the absorptive and secretory unidirectional Cl(-) fluxes was observed in basal conditions, but after STa stimulation, a significant net secretory Cl(-) flux developed. We conclude that, under these conditions, the presence of secretory or absorptive J(w) values cannot be shown by I(sc) and ion flux studies. Furthermore, RT-PCR experiments indicate that aquaporins were not expressed in T84 cells. The molecular pathway for water secretion appears to be transcellular, moving through the lipid bilayer or, as recently proposed, through water-solute cotransporters.

Aquaporins↗

PubMed2000

Control of cell pH in the T84 colon cell line.

Cell pH regulation was investigated in the T84 cell line derived from epithelial colon cancer. Cell pH was measured by ratiometric fluorescence microscopy using the fluorescent probe BCECF. Basal pH was 7.17 +/- 0.023 (n = 48) in HEPES Ringer. After acidification by an ammonium pulse, cell pH recovered toward normal at a rate of 0.13 +/- 0.011 pH units/min in the presence of Na+, but in the absence of this ion or after treatment with 0.1 mm hexamethylene amiloride (HMA) no significant recovery was observed, indicating absence of Na+ independent H+ transport mechanisms in HEPES Ringer. In CO2/HCO3- Ringer, basal cell pH was 7.21 +/- 0.020 (n = 35). Changing to HEPES Ringer, a marked alkalinization was observed due to loss of CO2, followed by return to the initial pH at a rate of -0.14 +/- 0.012 (n = 8) pH/min; this return was retarded or abolished in the absence of Cl- or after addition of 0.2 mm DIDS, suggesting extrusion of bicarbonate by Cl-/HCO3- exchange. This exchange was not Na+ dependent. When Na+ was added to cells incubated in 0 Na+ Ringer while blocking Na+/H+ exchange by HMA, cell alkalinization by 0.19 +/- 0.04 (n = 11) pH units was observed, suggesting the presence of Na+/HCO3- cotransport carrying HCO3- into these cells, which was abolished by DIDS. These experiments, thus, show that Na+/H+ and Cl-/HCO3- exchange and Na+/HCO3- cotransport participate in cell pH regulation in T84 cells.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

PubMed2000

Water permeability in rat oocytes at different maturity stages: aquaporin-9 expression.

Important functional and structural modifications occur in mammalian oocytes during their arrival to maturity. In this process, oocytes switch from a high activity level, implying an important metabolic rate and a coordinated movement of water and solutes, to a lower functional state. The aim of this work was to study the mechanisms involved in water movements during oocyte arrival to maturity. Volume changes, induced by an osmotic gradient, were followed by video microscopy in rat oocytes. The water osmotic permeability (P(osm)) of immature oocytes (proestrus) was sensitive to HgCl(2) and phloretin. In contrast, mature oocytes (estrus) had a reduced P(osm) that was not sensitive to these compounds. When proestrus oocytes were incubated in vitro at 37 degrees C they spontaneously arrived at maturity and its P(osm) decreased between four and six hours of incubation. RT-PCR experiments were performed using specific primers for all rat aquaporins that had been cloned. We found that aquaporin-9 transcript (AQP9) is present in proestrus oocytes but not in estrus oocytes. AQP9 has been recently described as a "broad selective channel" responsible for solute and water transfers in highly active cells. Our experiments showed that proestrus oocytes, but not estrus, are permeable to mannitol. It is concluded that during the process of maturation, P(osm) decreases and AQP9 transcripts disappear. We report here the first study correlating water permeability and aquaporin mRNA expression in mammalian oocytes.

Animals↗

PubMed2000

Translational repression: a duet of Nanos and Pumilio.

Recent studies have shed new light on translational repression by Nanos and Pumilio proteins. The ancestral function of this repression mechanism appears to be in early germline development; later, species-specific applications in embryonic patterning and spermatogenesis-oogenesis switching evolved.

Animals↗

PubMed2000

Effects of medium hypertonicity on water permeability in the mammalian rectum: ultrastructural and molecular correlates.

Minute-by-minute net water fluxes (Jw) were measured across the isolated rectal epithelium in rats and rabbits. Five minutes after a serosal (but not mucosal) hypertonic challenge (plus 200 mosmol/l) a significant increase in the basal Jw was recorded in both species [deltaJw, microl min(-1) cm(-2): 0.40+/-0.06 (rats); 0.45+/-0.10 (rabbits)]. At the same time, most epithelial cells shrank markedly while the intercellular spaces were wide open (electron microscopy studies). In freeze-fracture studies multi-strand tight-junction structures (only slightly modified by serosal hypertonicity in rabbits) were observed in control conditions. No structural changes were observed after mucosal hypertonicity (both in rats and rabbits). Immunohistochemical studies showed the expression of aquaporin 3 (AQP3) at the basolateral membrane of epithelial cells in the rat. A first conclusion is that the epithelium of the mammalian rectum is a highly polarized, aquaporin-3-containing, water permeability structure. The Jw increase induced by serosal hypertonicity was sensitive to mercurial agents in both species and no changes in unidirectional [14C]mannitol fluxes (Ps) or transepithelial resistance (RT) were observed during this Jw increase. These observations suggest a transcellular route for the osmotically induced increase in water fluxes. In the rabbit rectum the initial Jw response, associated with serosal hypertonicity, was a transient one. It was followed by a second, slow and HgCl2-sensitive Jw increase (a transient peak in paracellular mannitol permeability was also observed). A second conclusion is that serosal hypertonicity induces an increase in transcellular water permeability in both rat and rabbit rectum.

Animals↗

PubMed1999

The Drosophila pumilio gene encodes two functional protein isoforms that play multiple roles in germline development, gonadogenesis, oogenesis and embryogenesis.

The pumilio (pum) gene plays an essential role in embryonic patterning and germline stem cell (GSC) maintenance during oogenesis in Drosophila. Here we report on a phenotypic analysis using pum(ovarette) mutations, which reveals multiple functions of pum in primordial germ cell proliferation, larval ovary formation, GSC division, and subsequent oogenic processes, as well as in oviposition. Specifically, by inducing pum(-) GSC clones at the onset of oogenesis, we show that pum is directly involved in GSC division, a function that is distinct from its requirement in primordial germ cells. Furthermore, we show that pum encodes 156- and 130-kD proteins, both of which are functional isoforms. Among pum(ovarette) mutations, pum(1688) specifically eliminates the 156-kD isoform but not the 130-kD isoform, while pum(2003) and pum(4277) specifically affect the 130-kD isoform but not the 156-kD isoform. Normal doses of both isoforms are required for the zygotic function of pum, yet either isoform alone at a normal dose is sufficient for the maternal effect function of pum. A pum cDNA transgene that contains the known open reading frame encodes only the 156-kD isoform and rescues the phenotype of both pum(1688) and pum(2003) mutants. These observations suggest that the 156- and 130-kD isoforms can compensate for each other's function in a dosage-dependent manner. Finally, we present molecular evidence suggesting that the two PUM isoforms share some of their primary structures.

Animals↗

PubMed1999

PTEN mutation spectrum and genotype-phenotype correlations in Bannayan-Riley-Ruvalcaba syndrome suggest a single entity with Cowden syndrome.

Germline mutations in the tumour suppressor gene PTEN have been implicated in two hamartoma syndromes that exhibit some clinical overlap, Cowden syndrome (CS) and Bannayan-Riley-Ruvalcaba syndrome (BRR). PTEN maps to 10q23 and encodes a dual specificity phosphatase, a substrate of which is phosphatidylinositol 3,4,5-triphosphate, a phospholipid in the phosphatidylinositol 3-kinase pathway. CS is characterized by multiple hamartomas and an increased risk of benign and malignant disease of the breast, thyroid and central nervous system, whilst the presence of cancer has not been formally documented in BRR. The partial clinical overlap in these two syndromes is exemplified by the hallmark features of BRR: macrocephaly and multiple lipomas, the latter of which occur in a minority of individuals with CS. Additional features observed in BRR, which may also occur in a minority of CS patients, include Hashimoto's thyroiditis, vascular malformations and mental retardation. Pigmented macules of the glans penis, delayed motor development and neonatal or infant onset are noted only in BRR. In this study, constitutive DNA samples from 43 BRR individuals comprising 16 sporadic and 27 familial cases, 11 of which were families with both CS and BRR, were screened for PTEN mutations. Mutations were identified in 26 of 43 (60%) BRR cases. Genotype-phenotype analyses within the BRR group suggested a number of correlations, including the association of PTEN mutation and cancer or breast fibroadenoma in any given CS, BRR or BRR/CS overlap family ( P = 0.014), and, in particular, truncating mutations were associated with the presence of cancer and breast fibroadenoma in a given family ( P = 0.024). Additionally, the presence of lipomas was correlated with the presence of PTEN mutation in BRR patients ( P = 0.028). In contrast to a prior report, no significant difference in mutation status was found in familial versus sporadic cases of BRR ( P = 0.113). Comparisons between BRR and a previously studied group of 37 CS families suggested an increased likelihood of identifying a germline PTEN mutation in families with either CS alone or both CS and BRR when compared with BRR alone ( P = 0.002). Among CS, BRR and BRR/CS overlap families that are PTEN mutation positive, the mutation spectra appear similar. Thus, PTEN mutation-positive CS and BRR may be different presentations of a single syndrome and, hence, both should receive equal attention with respect to cancer surveillance.

Abnormalities, Multiple↗

PubMed1998

Reconstitution of a regulated transepithelial water pathway in cells transfected with AQP2 and an AQP1/AQP2 hybrid containing the AQP2-C terminus.

Transepithelial water permeability was measured in LLC-PK1 cells stably transfected with aquaporins (AQPs): AQP1, AQP2, and a chimera of AQP1 and AQP2 containing 41 amino acids of the C-terminus of AQP2. Transepithelial water fluxes (Jw) were not previously reported in cells transfected with aquaporins. Jw were now recorded each minute using a specially developed experimental device. A significant increase in Posm after forskolin (FK) plus vasopressin (VP) was found in AQP2 transfected cells (39.9 +/- 8.2 vs. 12.5 +/- 3.3 cm.sec-1.10(-3)), but not in cells transfected with AQP1 (15.3 +/- 3.6 vs. 13.4 +/- 3.6 cm.sec-1.10(-3)). In the case of the AQP1/2 cells (chimera) the FK plus VP induced Posm was smaller than in AQP2 cells but significantly higher than in mock cells at rest (18.1 +/- 4.8 vs. 6.7 +/- 1.0 cm.sec-1.10(-3)). The increases in Posm values were not paralleled by increases in 14C-Mannitol permeability. HgCl2 inhibited the hydrosmotic response to FK plus VP in AQP2 transfected epithelia. Results were comparable to those observed, in parallel experiments, in a native ADH-sensitive water channel containing epithelial barrier (the toad urinary bladder). Electron microscopy showed confluent LLC-PK1 cells with microvilli at the mucosal border. The presence of spherical or elongated intracellular vacuoles was observed in AQP2 transfected cells, specially after FK plus VP stimulus and under an osmotic gradient. These results demonstrate regulated transepithelial water permeability in epithelial cells transfected with AQP2.

Animals↗

PubMed1998

Effect of one-month treatment with nonsteroidal antiinflammatory drugs (NSAIDs) on gastric pH of rheumatoid arthritis patients.

The use of NSAIDs is strongly associated with peptic ulceration. The inhibition of prostaglandin synthesis with the consequent increase of gastric acidity is considered a possible mechanism. Therefore we decided to assess the effect of one-month treatment with NSAIDs on the circadian gastric pH of rheumatoid arthritis (RA) patients. We studied 11 consecutive patients (one man and 10 women, median age 55, range 26-72 years) with confirmed RA. None was H. pylori positive. A 24-hr gastric pH recording was performed both in basal conditions and after one-month treatment with either indomethacin 150 mg/day (eight cases) or ketoprofen 300 mg/day (three cases). Only the 10 female patients were eligible for final analysis, and six matched healthy subjects not taking NSAIDs were used as control group. The number of 24-hr pH readings for various pH thresholds was calculated for both populations. The highest acid levels (pH < 3.0) did not differ between the two pH profiles of the control group (7440 vs 7391, P = NS), while they predominated after the one-month NSAID treatment (10,339 vs 11,440, P < 0.001) in RA patients. These findings show that there is an increased gastric acidity after one-month of treatment with NSAIDs in female patients with RA of recent onset. This may sustain the rationale of using antisecretory agents to prevent gastroduodenal ulcerations in these patients.

Administration, Oral↗