Search PubMed⌕ Search

Biomedical subjects

P Ruiz

Publications and source records attributed to P Ruiz.

At least 271 records · Page 15Linked to original sources
PubMed1989

Association of chronic thromboxane inhibition with reduced in situ cytotoxic T cell activity in rejecting rat renal allografts.

The development of allospecific cellular immunity during acute rat renal allograft rejection parallels alterations occurring in arachidonic acid metabolism, including increased production of the vasoconstrictor eicosanoid thromboxane A2 (TxA2). We have previously demonstrated that chronic inhibition of thromboxane synthetase is associated with improved renal allograft function as well as significant reductions in renal production and urinary excretion of Tx metabolites. In this study, we evaluated the effects of chronic administration of the specific Tx synthetase inhibitor OKY-046 on in situ and systemic alloimmune effector cell function. PVG (RT1c) strain rats were transplanted with fully allogeneic ACI(RT1a) kidneys, and intrarenal artery infusion of OKY-046 (50 micrograms/mg/min) or its saline vehicle was begun at the time of surgery utilizing an osmotic pump. Four days following transplantation, spleen cells and inflammatory cells eluted from the graft were tested. The frequency of antidonor precursor cytotoxic T cells (pCTL), as measured by limiting dilution assay, was consistently lower in allografts from OKY-046-treated animals (1/3146-1/5160) compared with vehicle treatment (1/661-1/1878), while no difference in pCTL ranges were seen in splenocytes from both groups. However, following short-term culture (10-15 days, lymphocytes from treated and control allografts were equally proficient in specifically lysing donor targets. Proliferative response to donor stimulators measured by mixed lymphocyte reaction assays were consistently greater in spleen cells than allograft eluate cells for both groups, but there were no significant differences between OKY and vehicle groups in terms of either splenocyte or allograft eluate proliferative responses. Immunohistologic labeling and flow cytometric analysis of renal allograft infiltrates showed similar percentages and distributions of immune cell populations in treated and control groups. These results suggest that Tx inhibition is capable of temporarily reducing cytotoxic T cell function in the local environment, which may partially account for the improved graft function seen.

Animals↗
PubMed1989

High-protein feeding stimulates renal thromboxane production in rats with streptozocin-induced diabetes.

In diabetic rats glomerular morphologic damage is exacerbated by feeding a protein-rich diet. Protein feeding alters arachidonic acid metabolism in other models of renal disease, and there is evidence that the arachidonic acid metabolite thromboxane plays a pathophysiologic role in protein-induced renal injury. In this study we evaluated the effect of high-protein feeding on renal thromboxane production, renal hemodynamics, and renal morphologic condition in rats with experimentally induced diabetes. We induced diabetes in male Sprague-Dawley rats by streptozocin administration. Rats then received high (60% casein)- or low (8% casein)-protein diets. Eight to 11 weeks later, clearance of inulin and PAH and renal blood flow were measured. Rats fed 60% casein had higher glomerular filtration rate and renal blood flow than rats fed low-protein diets. Rats fed high-protein diets had more glomerular hypercellularity, tubular hypertrophy, and arteriolar thickening than their protein-restricted counterparts. Renal production of 6-keto-PGF1a and PGE2 was not different between dietary groups. Renal thromboxane production, however, was greater in rats fed 60% protein than in rats fed 8% protein. We conclude that protein feeding stimulates renal thromboxane production and exacerbates morphologic injury in the diabetic rat. Short-term administration of the thromboxane synthetase-inhibitor UK 38,485 did not further increase glomerular filtration rate or renal blood flow in animals fed high protein. Thus thromboxane did not appear to play a role in protein-induced injury in this model by a vasoconstrictive mechanism. Other possible mechanisms by which thromboxane may contribute to the renal damage observed are discussed.

Animals↗
PubMed1988

Evidence that pretransplant donor blood transfusion prevents rat renal allograft dysfunction but not the in situ cellular alloimmune or morphologic manifestations of rejection.

The effects of preoperative donor-specific blood transfusion (DSBT) on the physiologic, morphologic, and immunologic aspects of allograft responsiveness were evaluated in a rat renal transplant model, using the ACI (RT1a) into PVG (RT1c) high-responder strain combination. Indefinite graft survival (mean greater than 63 days) could be induced by DSBT administration alone. In comparison, animals receiving autologous blood transfusion (ABT) all died within 7 days posttransplantation. As assessed by clearance of inulin and paraaminohippurate, renal allograft function in DSBT-pretreated recipients at 6 days was equivalent to that of isograft recipients, and in contrast to the significant reduction seen in ABT treated rats. Likewise, thromboxane B2 (TXB2) production by ex-vivo-perfused allografts from DSBT-treated recipients was comparable to that of isografts, and significantly lower than that of allografts from ABT-treated rats. A significant inverse correlation was found between renal TXB2 production and inulin clearance. Despite these substantial differences in renal function and eicosanoid metabolism, morphologic evaluation of renal allografts from DSBT-enhanced and ABT-rejecting recipients at comparable time points showed equivalent histologic manifestations of rejection. In addition, immunohistologic labeling of renal allograft sections and fluorescence-activated cell sorter analysis of cells eluted from allografts showed the same phenotype and pattern of infiltrating T cell subsets in both groups. Specific antidonor cytotoxic T lymphocyte precursor (pCTL) frequencies of cells eluted from kidney grafts were equivalent in DSBT and ABT-pretreated animals, and both groups expressed significantly higher (but equivalent) pCTL frequencies in the kidneys than spleens. Comparisons of the lysis of PVG.R1 (RT1.Aa on a PVG background) and ACI targets indicated that cytotoxic responses from effector cells freshly eluted from DSBT and ABT kidneys were primarily directed against allogeneic class I major histocompatibility complex (MHC) specificities, whereas several long term T cell lines generated from 6-day kidney transplants of both groups expressed a predominant W3/25+ (T helper) phenotype and cytotoxic activity against donor specificities other than RT1.Aa class I MHC. Specific antidonor proliferative T lymphocyte (pPTL) precursor frequencies of cells eluted from renal allografts were also equivalent for both DSBT- and ABT-treated recipients, and the range of pPTL frequencies for allograft cell eluates was similar to that in spleens, regardless of the source of the transfusion.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1988

Associations between cyclosporine therapy and interstitial fibrosis in renal allograft biopsies.

A retrospective masked study of 120 consecutive renal transplant biopsies was performed to evaluate the potential associations of cyclosporine (CsA) therapy and other factors on the degree and progression of interstitial fibrosis (IF). Allograft biopsies were obtained from patients receiving CsA (CsA+; n = 59) and not receiving CsA (CsA-; n = 46); pretransplant donor biopsies were used as controls (n = 15). IF was evaluated by histologic grading (0-3+) as well as by quantitative morphometric measurements of Masson's trichrome stain positive material. Other biopsy measurements included the pattern of IF (focal, diffuse; graded 0-3+), and tubular epithelial cell reactivity, necrosis, and vacuolization (each graded 0-3+). Potential confounding variables were also considered, including time interval between transplant and biopsy; creatinine levels at the time of biopsy, 2 weeks and 10 weeks postbiopsy, and the last stable (baseline) creatinine prior to biopsy; recipient age, clinical evidence of rejection, and duration of rejection reactions; transplant number; and postbiopsy graft outcome. No significant difference in any measure of IF was found between all CsA+ vs. CsA- patients, although both groups showed a highly significant increase in IF compared with control pretransplant donor biopsies. Similarly, no differences in tubular changes or the patterns of fibrosis were identified between CsA groups. However, since the mean interval between transplant and biopsy was significantly (P less than 0.04) greater for the CsA- group, measures of creatinine and IF were normalized by the time interval between transplant and biopsy, and were stratified into biopsies obtained before or after 6 months posttransplant. By this stratification and normalization, both the baseline creatinine (P less than 0.01) and the degree of IF as measured by morphometry (P less than 0.04) were significantly higher in the CsA+ group, but only for biopsies obtained greater than 6 months posttransplant. Evaluation of biopsies less than 6 months posttransplant normalized by interval showed no suggested differences between the CsA+ and CsA- groups in terms of creatinine levels or any measure of IF. Tubular epithelial changes were not different in the CsA+ and CsA- groups within either period. These results suggest that CsA therapy is not associated with increased interstitial fibrosis in renal allografts prior to 6 months posttransplant, after which there is a significant increase in fibrosis relative to patients not receiving CsA.

Biopsy↗
PubMed1987

In vitro susceptibility of Mycobacterium tuberculosis to a new macrolide antibiotic: RU-28965.

The in vitro susceptibility of Mycobacterium tuberculosis to a new macrolide antibiotic RU-28965, alone and in combination with rifampicin or isoniazid, was studied by the agar dilution method. At a concentration of 4 mg/l, or lower, of RU-28965, 90% of the strains were inhibited. A synergistic effect with both rifampicin and with isoniazid was demonstrated.

Antibiotics, Antitubercular↗
PubMed1987

In vitro susceptibility of Mycobacterium tuberculosis to ofloxacin and ciprofloxacin in combination with rifampin and isoniazid.

The in vitro susceptibility of Mycobacterium tuberculosis to new quinolones, ofloxacin and ciprofloxacin, alone and in combination with rifampin or isoniazid, was studied by the agar dilution method. At a concentration of 1 mg/l or lower of ofloxacin and ciprofloxacin, 90% of the strains were inhibited. A synergistic effect with rifampin and with isoniazid was demonstrated.

Anti-Bacterial Agents↗
PubMed1986

Vascular renin-like activity in aorta and mesenteric artery of the rat.

Vascular renin-like enzymatic activity (VRLA) has been measured in the artery wall of control and experimental rats. The following groups have been studied: 1-normal salt diet; 2-high salt diet; 3-low salt diet; 4-bilateral nephrectomy (Nx); 5-sham operated for Nx. VRLA was evaluated in the aorta (ARLA) and in the mesenteric arteries (MRLA). Blood samples were obtained for plasma renin activity (PRA) determination. High salt diet decreased PRA, ARLA and MRLA whereas low salt diet increased PRA, did not change ARLA and decreased MRLA. PRA was almost undetectable in Nx animals while ARLA showed a 40% reduction and MRLA was unchanged in these animals. These results would indicate that the changes in PRA induced different variations in the renin-like content of the aorta and the mesenteric artery. The differences could be mainly due to two factors: 1) the capacity of the vascular tissue to bind circulating renin and 2) the capacity of each tissue to synthetize renin-like material in situ.

Animals↗
PubMed1985

Cultural barriers to effective medical care among Hispanic-American patients.

In attempting to successfully diagnose and treat people from different cultural dimensions, medical practitioners must supplement theoretical concepts with knowledge about the patients' cultural heritage. In this chapter, the author discusses relevant cultural factors related to the medical management of Cubans, Puerto Ricans, and Mexican Americans residing in the United States.

Acculturation↗
PubMed1985

The brain renin-angiotensin system and the development of DOC-salt hypertension.

UNLABELLED: The effect of captopril, given in the drinking fluid, on the development of DOC-salt hypertension was analyzed. Although captopril did not prevent an increase in blood pressure (BP) elicited by DOC-salt, captopril did diminish BP in both DOC-salt and control animals. From the first week of treatment DOC-salt rats increased their fluid intake (FI). At the end of the experiment, captopril reduced this increment (655% to 357%). At the same time plasma angiotensinogen was diminished (-35%; p less than 0.001) and cerebrospinal fluid (CSF) substrate concentration increased (+33%; p less than 0.02) in DOC-salt rats, captopril did not modify these changes. In control rats captopril did not alter FI, depleted plasma angiotensinogen, (-73%; p less than 0.001), did not change the central prohormone and increased plasma renin activity (PRA) (+260%; p less than 0.001). IN CONCLUSION: CSF angiotensinogen concentration changes as previously found in CNS while a clear dissociation between plasma and CSF angiotensinogen was found in DOC-salt rats. In these animals the hypertension was not clearly affected by captopril treatment. However the effect of the converting enzyme inhibitor suggests that the central renin-angiotensin system could participate in the increase in FI.

Angiotensinogen↗
PubMed1985

Renin-like activity in vascular tissue of DOC-salt hypertensive rats.

The presence of isorenin active at the physiological pH was investigated in DOC-salt hypertensive rats. The effect of chronic captopril treatment was analyzed in similarly treated animals and in control rats. The levels of the plasma (PRA) and vascular enzyme (VRLA) were compared with those of untreated control animals. DOC-salt administration was maintained during 4 or 8 weeks. Captopril was given in the drinking fluid beginning 4 days before DOC-salt treatment. Renin-like activity was measured in the aorta and mesenteric arteries. DOC-salt treatment reduced PRA to almost undetectable levels while aorta renin-like enzyme only decreased to 50% at 4 weeks and was not changed at 8 weeks. Isorenin levels in the mesenteric artery did not show any significant variation. Captopril did not prevent the increase in blood pressure due to DOC-salt administration and it induced a significant increase in PRA and in VRLA in control rats whereas it did not increase either - enzyme in DOC-salt treated rats. In summary these results confirm the existence of a vascular isorenin and suggest that both binding and local synthesis of the enzyme could take place in the arterial wall.

Angiotensin-Converting Enzyme Inhibitors↗