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PubMed1997

Alpha 5 subunit forms functional alpha 3 beta 4 alpha 5 nAChRs in transfected human cells.

nAChRs heterologously expressed in human cells after transient transfection with alpha 3 beta 4 alpha 5 or alpha 3 beta 4 subunit cDNAs exhibited similar sensitivities to antagonists and comparable functional channel profiles. However, the sum of two Hill equations was required for best fitting the ACh dose-current response curves after co-expression of alpha 5, alpha 3 and beta 4 subunits. One component was comparable to that obtained in alpha 3 beta 4-transfected cells, while the additional component, putatively attributed to an alpha 3 beta 4 alpha 5 nAChR population, showed a Hill coefficient > 2 and a nine-fold greater half-maximal ACh concentration (EC50). These results suggest that the alpha 5 subunit participates in the assembly of alpha 3 beta 4 alpha 5 nAChRs complexes in human cells, adding a new member to the family of neuronal nicotinic receptors.

Acetylcholine↗
PubMed1999

Impaired glucose tolerance, beta cell function and lipid metabolism in HIV patients under treatment with protease inhibitors.

OBJECTIVES: To evaluate metabolic abnormalities, beta-cell function, lipid profile and vascular risk factors in HIV patients on protease inhibitors (PI). DESIGN: Prospective cross-sectional study. METHODS: Thirty-eight HIV-1-infected patients receiving at least one PI were compared with 17 PI-naive HIV patients in an oral glucose tolerance test (OGTT). Serum glucose, insulin, proinsulin, and C-peptide were determined. The fasting lipid pattern was analysed using electrophoresis and the assessment of apolipoproteins including lipoprotein (a). Fibrinogen, homocysteine, and anticardiolipin antibodies were also assessed. RESULTS: Twenty-seven (71%) of the PI-treated group had detectable hyperlipidaemia. Isolated hypertriglyceridaemia was present in 12 patients (44%), two (7%) of them had type V and 10 (37%) subjects had type IV hyperlipidaemia (Frederickson classification). Type IIb hyperlipidaemia defined as an increase of both very-low-density lipoproteins (VLDL) and low-density lipoproteins (LDL) was found in 10 (36%) subjects, and five (18%) patients presented with isolated hypercholesterolaemia (type IIa). PI treatment was associated with significant higher fasting cholesterol, triglycerides, LDL and VLDL levels. Apolipoprotein B and E concentrations were significantly increased in patients receiving PI. Elevated concentrations of lipoprotein (a) (> 30 mg/dl) were detected in six (16%) of the hyperlipidaemic patients on PI. Eighteen (46%) patients on PI had impaired oral glucose tolerance and five (13%) had diabetes. Although four (24%) of the PI-naive patients were glucose intolerant, none had diabetes. Fasting concentrations and secretion response of insulin, proinsulin, and C-peptide to glucose ingestion was significantly increased in the PI-treated group suggesting a beta-cell dysfunction in addition to peripheral insulin resistance. Beta-cell abnormalities were associated with the abnormal lipid pattern and PI treatment. CONCLUSION: Combination drug regimens including PI are accompanied by impaired glucose tolerance, hyperproinsulinaemia as an indicator for beta-cell dysfunction, and lipid abnormalities proved to be significant risk factors for coronary heart disease. Moreover, PI may have an impact on the processing of proinsulin to insulin.

Adult↗
PubMed1981

Effect of sodium nitroprusside on postoperative blood loss in the cardiac surgical patient.

Sodium nitroprusside (SNP) is known to inhibit platelet aggregation and has been implicated in postoperative hemorrhagic complications. Because it is a useful agent for treating postoperative hypertension and low cardiac output in the cardiac surgical patient, the authors retrospectively reviewed the course of 53 patients undergoing open heart procedures on cardiopulmonary bypass. Twenty-three patients received SNP and 30 did not. There were no differences in baseline hematological or clotting profiles, liver functions, bypass or cross-clamping times or heparin/protamine requirements between the two groups. Analysis revealed no significant differences between the groups in blood product requirements, actual mediastinal drainage, or postoperative measurements of routine clotting parameters. Although biochemical inhibition of platelet aggregation can be demonstrated, the use of SNP in the cardiac surgical patient has no apparent clinical effects which sould detract from its utility in treating hypertension or low cardiac output.

Cardiac Output, Low↗
PubMedDate not supplied

Impact on patients and partners of inpatient and extended cardiac counseling and rehabilitation: a controlled trial.

OBJECTIVES: This study evaluated the effectiveness of cardiac counseling and rehabilitation programs led by a nurse counselor, compared with normal care on outcomes for myocardial infarction (MI) patients and their partners. METHODS: A randomized controlled trial with follow-up to 1 year was conducted with 100 patients recruited within 72 hours of a first MI and their partners: a Control group received normal care; an Inpatient group received cardiac rehabilitation from a nurse counselor while in hospital; and an Extended group received the same cardiac rehabilitation as the Inpatient group, but with additional sessions continuing up to 6 weeks after discharge from hospital. The scales for main outcome measures were 1) knowledge of heart disease and treatment (correct, misconceptions, and uncertainty); 2) mood (Hospital Anxiety and Depression Scale); 3) satisfaction; 4) disability (Functional Limitations Profile). RESULTS: Inpatient cardiac counseling and rehabilitation resulted in more knowledge, less anxiety, less depression, and greater satisfaction with care in both patients and partners and in less disability in patients, with effects enduring to 1 year. There was some evidence of additional benefit from the Extended program. Both nurse counselors achieved benefits on all outcome variables. CONCLUSIONS: This Inpatient cardiac counseling and rehabilitation program resulted in significant and enduring benefits of clinical value. It is likely that it would be acceptable to most post-MI patients, many of whom are not offered or are unable to accept outpatient cardiac rehabilitation.

Aged↗
PubMed1983

Increased free plasma corticosterone and adrenal hyperactivity associated with graft-versus-host disease.

This study profiles adrenal function in 14-day-old neonatal and adult rats with graft-versus-host disease (GVHD). Measurements of adrenal function included total serum corticosterone, the relative percentage of free corticosterone (a measure of biologically active hormone), adrenal cholesterol content, adrenal weights, and adrenal histology. Diseased animals in both age groups displayed a shift from the protein-bound to the free corticosterone fraction, with, surprisingly, no change in total serum corticosterone titers. We discuss the possibility that such a shift toward the biologically active, free-hormone pool results in a physiologic hyperglucocorticoidism that might contribute to the progress of GVHD. Compared with littermate controls, diseased adults had enlarged adrenals. In neonates with GVHD, no adrenal hypertrophy was evident, yet decreased adrenal cholesterol content and associated depletion of adrenal lipid droplets--evidence of adrenal hyperactivity--were identified. The GVHD must be responsible for the observed alterations in adrenal function because treatment of affected animals with alloantiserum directed against donor cells halted the disease and elevated the cholesterol content toward control levels. The possible contribution of adrenal dysfunction to the pathogenesis of secondary manifestations of GVHD is discussed.

Adrenal Glands↗
PubMed2003

Cross-species costimulation: relative contributions of CD80, CD86, and CD40.

BACKGROUND: The response of human CD4+ T cells against porcine cells is of comparable magnitude to that induced by human leukocyte antigen-mismatched allogeneic cells. This reflects productive interactions between key costimulatory molecules across the species barrier. Inhibition of these molecular interactions will be crucial in overcoming CD4+ T-cell-mediated rejection of xenografts. We have performed a detailed investigation to determine the expression profiles and relative contributions of the three key costimulatory molecules in the porcine-human xenogeneic response. Whereas only porcine CD86 is constitutively expressed on resting endothelial cells, both CD40 and CD80 are rapidly expressed after activation. All three costimulatory molecules are expressed by professional antigen-presenting cells. METHODS: We have isolated full-length cDNA clones for human and porcine CD80, CD86, and CD40. Human fibroblast cell lines (M1) coexpressing DR1 were transfected with these cDNAs and used in mixed lymphocyte reactions and flow cytometric studies in vitro. RESULTS: These data provide the first characterization of the expression profile and functional role of porcine CD80. Functional assays demonstrate that pCD40, pCD80, and pCD86 are independently capable of costimulating human CD4+ T cells, albeit with differing kinetics. Proliferative responses were of comparable magnitude to those obtained when costimulation was provided by human CD40, CD80, and CD86. CONCLUSIONS: These data have implications for therapy targeting the direct pathway of xenorecognition; costimulatory molecule blockade must be directed against both the B7/CD28 and CD40/CD40L pathways.

Animals↗
PubMed2026

Comparative Effectiveness of Pharmacogenomics for Treatment of Depression.

PURPOSE/BACKGROUND: Pharmacogenomics (PGx), or the use of genetic information to assess drug-gene interactions, is an important step toward precision medicine. It is unclear if clinician use of PGx yields better outcomes for their patients. This study compared the effectiveness of combinatorial PGx-guided plus guideline-informed treatment (PGx+GIT) with guideline-informed treatment (GIT) alone to improve well-being in individuals with major depressive disorder. METHODS/PROCEDURES: Eligible participants (N=201) were randomized to PGx+GIT or GIT alone. PGx was measured with the proprietary GeneSight combinatorial test. PGx+GIT participant clinicians received test results within 2 business days to inform decisions about medication changes. Participants completed the World Health Organization Well-Being Index (WHO-5), Patient Health Questionnaire (PHQ-9), and PROMIS Profile physical functioning and social roles and activity domains every 2 weeks for 2 months and then every 2 months for the remaining 10 months. Monthly medication changes operationalized as necessary clinical adjustments were tracked with the medication recommendation tracking form. FINDINGS/RESULTS: Both groups improved average well-being over the 12-month study period (model-based change in WHO-5 per log (week) [95% CI]: 4.1 [3.3, 5.0] PGx+GIT and 4.8 [4.0, 5.5] GIT). PGx+GIT did not result in superior improvement in well-being (model-based difference [95% CI]: -0.6 [-1.8, 0.5], P =0.270), or any secondary outcomes. The effect of randomized treatment on well-being was not moderated by depression severity, number of previous failed medications for major depressive disorder, or presence of a comorbid condition. IMPLICATIONS/CONCLUSIONS: These data suggest PGx+GIT was not superior to GIT alone, possibly due to a ceiling effect of GIT, or PGx did not yield better results.

Humans↗
PubMed2007

Allergic bronchopulmonary aspergillosis: an Indian perspective.

PURPOSE OF REVIEW: Allergic bronchopulmonary aspergillosis is an immunologically mediated lung disease that is caused by hypersensitivity to antigens of the genus Aspergillus. This review summarizes the clinical presentation, radiologic profile, lung functions and immunologic studies on allergic bronchopulmonary aspergillosis from India. Data regarding Aspergillus sensitization in asthmatics are presented. The association of allergic bronchopulmonary aspergillosis with allergic Aspergillus sinusitis and aspergilloma is also highlighted. RECENT FINDINGS: Allergic bronchopulmonary aspergillosis is now an emerging disease in India. Sensitization to Aspergillus antigens is not uncommon in our patients with asthma. Although asthma commenced in these subjects in their early 20s, allergic bronchopulmonary aspergillosis was recognized more than a decade later. Allergic bronchopulmonary aspergillosis can also occur in patients without clinical asthma. Radiology is crucial to the diagnosis of allergic bronchopulmonary aspergillosis. The remarkable radiological similarity to pulmonary tuberculosis has important clinical implications in our country as patients with allergic bronchopulmonary aspergillosis often receive antituberculous therapy for a long time. Although oral corticosteroids still remain the cornerstone for management, itraconazole has emerged as an adjunct therapy in appropriate situations. Concomitant occurrence of allergic bronchopulmonary aspergillosis and allergic Aspergillus sinusitis is now being increasingly recognized. SUMMARY: All asthmatic subjects with a positive skin prick test to Aspergillus antigens must be evaluated for allergic bronchopulmonary aspergillosis and allergic Aspergillus sinusitis should be excluded.

Adrenal Cortex Hormones↗
PubMed1999

Functional antibody response to human cytomegalovirus in immunocompetent and HIV-1 infected individuals with antibodies that inhibit virus penetration into cells and intercellular transmission of viral infection.

Antibodies mediating post-attachment virus neutralisation (PN), inhibition of human cytomegalovirus (HCMV)-induced cell fusion in the glioblastoma cell line U373 (IF) and global neutralising activity (NA) were quantified in sera from healthy immunocompetent individuals, asymptomatic HIV-1-infected subjects and AIDS patients to further characterise the neutralising antibody response to HCMV in these population groups and to assess whether HIV-1-infected individuals exhibited an abnormal functional antibody profile. PN and IF antibodies accounted for a minor fraction of the NA activity of sera from all population groups. Sera from HIV-1-infected individuals (particularly AIDS patients) displayed higher levels of PN and IF antibodies than those from the healthy control group; however, the relative contribution of these antibodies to the global serum NA activity appeared to be lower in the former individuals than in immunocompetent controls. Serum antibodies preventing HCMV cell-to-cell spread (IP) were then measured to determine whether a specific deficiency could be detected in the HIV-1-infected group population. Serum IP antibody titres were significantly higher in HIV-1-infected individuals (particularly in AIDS patients) than in controls. The potential implications of the data for explaining the pathogenesis of HCMV infection are discussed.

Acquired Immunodeficiency Syndrome↗
PubMed2026

Transcriptomic and proteomic signatures underlying nymphal adaptation and foam production in the forage pest Mahanarva spectabilis.

The spittlebug Mahanarva spectabilis (Distant, 1909) (Hemiptera: Cercopidae) is an important pest of forage grasses in South America, where its nymphs cause pasture damage by feeding on xylem sap and producing a characteristic foam that protects them against environmental stressors. To investigate the molecular basis of this adaptation, we integrated RNA-seq analysis of nymphs with LC-MS/MS proteomics of the Batelli gland, the primary source of foam secretion. De novo assembly of 100,666 unigenes revealed broad functional diversity, with strong representation of detoxification enzymes (CYP450s, GSTs, UGTs, carboxylesterases), transporters and ion pumps, cuticle proteins, and stress- and immunity-related genes. Nearly 16% of loci exhibited alternative splicing, particularly within detoxification, chemosensory and osmoregulatory gene families, highlighting evidence of transcriptomic variability. Signal peptide and secreted protein predictions identified 168 high-confidence candidate secreted proteins, including detoxification enzymes, proteases, structural proteins and immune-related factors, several of which are consistent with antimicrobial and surfactant-related functions. Proteomic profiling of the Batelli gland confirmed 500 proteins, enriched in chaperones, metabolic enzymes, detoxification pathways and osmoregulatory components, with the most abundant proteins corresponding to Hsp70 chaperones, ATP synthases, cuticle proteins and carbonic anhydrases. Together, these results provide an integrative transcriptomic and proteomic overview for M. spectabilis nymphs, highlighting genes and proteins associated with xylem feeding, foam production and responses potentially related to environmental stress tolerance. This comprehensive dataset not only advances the understanding of spittlebug biology but also identifies candidate molecular targets that may inform innovative strategies for controlling nymphal stages and mitigating spittlebug damage in forage systems.

Animals↗
PubMed2005

International conference on the healthy effect of virgin olive oil.

1. Ageing represents a great concern in developed countries because the number of people involved and the pathologies related with it, like atherosclerosis, morbus Parkinson, Alzheimer's disease, vascular dementia, cognitive decline, diabetes and cancer. 2. Epidemiological studies suggest that a Mediterranean diet (which is rich in virgin olive oil) decreases the risk of cardiovascular disease. 3. The Mediterranean diet, rich in virgin olive oil, improves the major risk factors for cardiovascular disease, such as the lipoprotein profile, blood pressure, glucose metabolism and antithrombotic profile. Endothelial function, inflammation and oxidative stress are also positively modulated. Some of these effects are attributed to minor components of virgin olive oil. Therefore, the definition of the Mediterranean diet should include virgin olive oil. 4. Different observational studies conducted in humans have shown that the intake of monounsaturated fat may be protective against age-related cognitive decline and Alzheimer's disease. 5. Microconstituents from virgin olive oil are bioavailable in humans and have shown antioxidant properties and capacity to improve endothelial function. Furthermore they are also able to modify the haemostasis, showing antithrombotic properties. 6. In countries where the populations fulfilled a typical Mediterranean diet, such as Spain, Greece and Italy, where virgin olive oil is the principal source of fat, cancer incidence rates are lower than in northern European countries. 7. The protective effect of virgin olive oil can be most important in the first decades of life, which suggests that the dietetic benefit of virgin olive oil intake should be initiated before puberty, and maintained through life. 8. The more recent studies consistently support that the Mediterranean diet, based in virgin olive oil, is compatible with a healthier ageing and increased longevity. However, despite the significant advances of the recent years, the final proof about the specific mechanisms and contributing role of the different components of virgin olive oil to its beneficial effects requires further investigations.

Aging↗
PubMed2004

Abnormal glucose tolerance--a common risk factor in patients with acute myocardial infarction in comparison with population-based controls.

BACKGROUND: A high prevalence of newly detected diabetes and impaired glucose tolerance (abnormal glucose tolerance) was recently reported in patients with acute myocardial infarction. It is important to verify whether this finding is specific for the patients or attributable to the population, from which they were recruited. OBJECTIVE: To verify whether abnormal glucose tolerance is more prevalent in patients than in controls chosen from the same population and to compare metabolic characteristics between the two groups. DESIGN AND SUBJECTS: The metabolic state was assessed in patients (n = 181) admitted with acute myocardial infarction and no history of diabetes before discharge and after 3 months. Sex- and age-matched controls (n = 185) without previously known diabetes or cardiovascular disease except hypertension were recruited from the general population. MAIN OUTCOME MEASURES: Oral glucose tolerance test, glucosylated haemoglobin A1c (HbA1c), insulin, proinsulin, lipid profile, fibrinolytic function and inflammatory markers. RESULTS: Abnormal glucose tolerance was more common (number/all classified) in patients at discharge 113/168 (67%) and after 3 months 95/145 (66%) than in controls 65/185 (35%) (P < 0.001). Dyslipidaemia (70% vs. 29%; P < 0.001) and previously treated hypertension (32% vs. 18%; P = 0.028) were more frequent amongst patients whilst obesity (18% vs. 24%) did not differ significantly. Blood glucose, HbA1c, proinsulin, proinsulin/insulin ratio, triglycerides, insulin resistance (by HOMA) and fibrinogen were consistently higher in patients than controls (P < 0.01). CONCLUSIONS: Abnormal glucose tolerance was almost twice as common amongst patients with acute myocardial infarction as in matched controls. Impaired glycaemic control accompanied by insulin resistance, dyslipidaemia, hypertension, together with increased plasma fibrinogen and proinsulin levels were main features characterizing patients.

Acute Disease↗
PubMed2006

Distribution of hepatitis C virus genotypes in beta-thalassaemic patients from Northern India.

Multitransfused beta-thalassaemic patients constitute a population having a higher prevalence of hepatitis C virus (HCV) infection because of its transmission from infected blood collected during seronegative window period. HCV genotyping in thalassaemic patients is mainly useful for the clinical management of the patients and for facilitating decisions on therapy. Thus, the aim of the present study was to identify the genotypes that are prevalent in thalassaemic patients and to correlate these with gender, age, number of blood transfusions and the liver function test profiles. Reverse transcription-polymerase chain reaction (RT-PCR) was carried out in 80 beta-thalassaemic patients (58 men and 22 women) for detection of HCV RNA who were seronegative for hepatitis B virus or human immunodeficiency virus antibodies. HCV genotyping was carried out by restriction fragment length polymorphism (RFLP) method of Chinchai et al. Type-specific PCR followed by direct sequencing was also used to confirm the mixed-genotype infection. Among the 80 thalassaemic patients, 20 and eight patients were infected with genotypes 3 and 1, respectively, whereas two cases had infection with HCV genotype1c/5a. The serum levels of aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase were found to be significantly altered between the two groups of HCV-infected and noninfected thalassaemic patients. No significant correlation was observed between genotypes when compared with gender, age and number of blood transfusions, except significantly higher level of ALP in genotype 1 than in genotype 3. Genotype 3 alone was the predominant type in beta-thalassaemic patients, with approximately 45% being infected with mixed type. Hence, detection of HCV RNA would help in decreasing the transmission of HCV-infected blood collected during the seronegative window period, whereas determination of genotypes would provide help in adoption of different treatment policies for better management of thalassaemic patients.

Adolescent↗
PubMed2005

Morphological and functional differences in haemostatic axis between kidney transplanted and end-stage renal disease patients.

End-stage renal disease (ESRD) is characterized by several atherothrombotic abnormalities, and kidney transplant seems to improve most of them. However, because it is not clear which mechanism is responsible for such improvement, our purpose was to clarify that point.We conducted a cross sectional study involving 30 ESRD patients, 30 ESRD kidney-transplanted patients (Ktx) and 30 healthy controls (C) to evaluate platelet morphology and function, atherothrombotic profile, endothelial abnormalities and cytokine levels involved in the insulin resistance/endothelial dysfunction. (i) Platelet morphology: The ESRD group showed platelet size similar to the other two groups (ESRD=3518x10(3)+/-549x10(3) nm2, C=3075x10(3)+/-197x10(3) nm2, Ktx=2862x10(3)+/-205x10(3) nm2) with similar platelet granules and number. (ii) Platelet surface glycoprotein: The CD41 and P-Selectin were similar between groups. (iii) Platelet intracellular calcium: Resting intracellular calcium was statistically higher in ESRD compared to the C group (ESRD=182.1+/-34.5, Ktx=126.7+/-14.1, C=72.0+/-11.0 nM, P<0.01). (iv) Hypercoagulability markers and natural anticoagulants: The Ktx and ESRD groups showed higher levels of hypercoagulability markers compared to the C group. A reduction in antithrombin activity was evident in ESRD compared to the Ktx group (P=0.03). (v) Endothelial morphology: The ESRD group showed a thickened vessel basal membrane compared to the Ktx and C groups with more endothelial sufference. (vi) Insulin resistance and pro-inflammatory cytokine profile: The ESRD showed a higher homeostasis model assessment provided equations for estimating insulin resistance (HOMA-IR) compared to the Ktx and C groups (ESRD=2.6+/-0.3, Ktx=1.8+/-0.2, C=1.1+/-0.1, P=0.005) and increased soluble tumor neurosis factor alpha (sTNFalpha) (P<0.05) and soluble vascular cell adhesion molecule (sVCAM) levels (P<0.01). Positive correlations were evident among HOMA-IR and sTNFalpha (P<0.001) and sVCAM (P=0.01), respectively. In a small subgroup of ESRD who underwent Ktx (five pts), our findings were confirmed at 1 year of follow-up, suggesting an improvement of almost haemostatic abnormalities. Kidney transplant is associated with a better atherothrombotic profile in ESRD, platelet intracellular calcium and cytokines seem to be most influenced by the transplant, while most morphological abnormalities are retained.

Adult↗
PubMed2006

Pathological study of Fitz-Hugh-Curtis syndrome evaluated from fallopian tube damage.

AIM: To analyze the causative pathogen, surgical indication and fallopian tube damages in Fitz-Hugh-Curtis syndrome (FHCS) cases diagnosed by laparoscopy. METHODS: Laparoscopic findings in 3568 cases at our hospital were reviewed retrospectively. Of these, 108 cases were diagnosed to have FHCS and examined for causative pathogens. Chlamydial infection was determined by both Chlamydia trachomatis (CT) antigens in the cervix and serum anti-CT antibodies. One hundred and four cases with chronic FHCS were divided into hydrosalpinx (H) and normal (N) groups based on the fallopian tube conditions, and were compared for patient profiles, tubal functions and perihepatic adhesion. RESULTS: Among surgical indications, tubal infertility and ectopic pregnancy were more often associated with FHCS than any other diseases. The primary causative pathogen of FHCS was CT. In 104 cases with chronic FHCS, there was no difference in CT antigen positivity between the H and N groups. The serum anti-CT IgG titer also did not differ between the two groups, although anti-CT IgA was slightly higher in the H group. The peritubal adhesion score was significantly higher in the H group, but it was not correlated with the degree of perihepatic adhesion. CONCLUSION: While some FHCS patients had severe fallopian tube dysfunctions, such as hydrosalpinx and tubal occlusion, 30% of FHCS cases did not show any abnormalities in the fallopian tube. Our study indicated that the severity of tubal dysfunctions associated with FHCS is determined by the host's reactivity to CT.

Adult↗
PubMed2004

AT-1 receptor blockade prevents proteinuria, renal failure, hyperlipidemia, and glomerulosclerosis in the Imai rat.

BACKGROUND: The Imai rat is a model of spontaneous focal glomerulosclerosis which leads to nephrotic syndrome, hyperlipidemia, hypertension, and progressive renal failure. We evaluated the effects of angiotensin II receptor type 1 (AT-1)blockade, and compared the results with the effects of the administration of hypolipidemic treatment with a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor. All treatments were started at 10 weeks of age when the rats were already proteinuric and continued for 6 months when rats were sacrificed. METHODS: The following groups (N= 6 each) were studied: (1) control Sprague-Dawley rats, 34 weeks old; (2) Imai group that received vehicle; (3) Imai + angiotensin II receptor blockade (ARB) group that received olmesartan (10 mg/kg/day by gastric gavage); (4) Imai + prava group, that received pravastatin (20 mg/kg/day by gastric gavage); and (5) Imai + ARB + prava group that received both ARB and pravastatin. Lipid profile, renal function, and structure were assessed at 6 months. RESULTS: As expected, the untreated Imai rats exhibited heavy proteinuria, hypoalbuminemia, hypertension, renal insufficiency, marked glomerulosclerosis, tubulointerstitial inflammation, and profound hyperlipidemia. Pravastatin treatment alone led to a significant, but partial improvement of hyperlipidemia and renal disease. The ARB treatment alone or in combination with pravastatin resulted in normalization of the blood pressure, urinary protein excretion, plasma cholesterol, triglycerides, low-density lipoproteins (LDLs), very low-density lipoproteins (VLDLs), and albumin concentrations and renal function. Significant glomerulosclerosis was prevented and tubulointerstitial injury and immune cell infiltration were reduced by long-term AT-1 blockade. CONCLUSION: The study revealed that long-term AT-1 blockade corrects proteinuria, hyperlipidemia, and nephropathy in this model of spontaneous glomerulosclerosis.

Angiotensin II Type 1 Receptor Blockers↗