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1.
Hypertension ; 81(6): 1345-1355, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38618734

ABSTRACT

BACKGROUND: Every year, thousands of patients with hypertension reduce salt consumption in an effort to control their blood pressure. However, hypertension has a self-sustaining character in a significant part of the population. We hypothesized that chronic hypertension leads to irreversible renal damage that remains after removing the trigger, causing an elevation of the initial blood pressure. METHODS: Dahl salt-sensitive rat model was used for chronic, continuous observation of blood pressure. Rats were fed a high salt diet to induce hypertension, and then the diet was switched back to normal sodium content. RESULTS: We found that developed hypertension was irreversible by salt cessation: after a short period of reduction, blood pressure grew even higher than in the high-salt phase. Notably, the self-sustaining phase of hypertension was sensitive to benzamil treatment due to sustaining epithelial sodium channel hyperactivity, as shown with patch-clamp analysis. Glomerular damage and proteinuria were also irreversible. In contrast, some mechanisms, contributing to the development of salt-sensitive hypertension, normalized after salt restriction. Thus, flow cytometry demonstrated that dietary salt reduction in hypertensive animals decreased the number of total CD45+, CD3+CD4+, and CD3+CD8+ cells in renal tissues. Also, we found tubular recovery and improvement of glomerular filtration rate in the postsalt period versus a high-salt diet. CONCLUSIONS: Based on earlier publications and current data, poor response to salt restriction is due to the differential contribution of the factors recognized in the developmental phase of hypertension. We suggest that proteinuria or electrolyte transport can be prioritized over therapeutic targets of inflammatory response.


Subject(s)
Blood Pressure , Disease Models, Animal , Hypertension , Rats, Inbred Dahl , Sodium Chloride, Dietary , Animals , Hypertension/physiopathology , Hypertension/etiology , Rats , Sodium Chloride, Dietary/adverse effects , Blood Pressure/physiology , Blood Pressure/drug effects , Male , Kidney/pathology , Kidney/drug effects , Kidney/metabolism , Epithelial Sodium Channels/metabolism , Diet, Sodium-Restricted
2.
Am J Physiol Renal Physiol ; 325(4): F418-F425, 2023 10 01.
Article in English | MEDLINE | ID: mdl-37560774

ABSTRACT

Inactivating mutations in the ALMS1 gene in humans cause Alström syndrome, characterized by the early onset of obesity, insulin resistance, and renal dysfunction. However, the role of ALMS1 in renal function and hemodynamics is unclear. We previously found that ALMS1 is expressed in thick ascending limbs, where it binds and decreases Na+-K+-2Cl- cotransporter activity. We hypothesized that ALMS1 is expressed in macula densa cells and that its deletion enhances tubuloglomerular feedback (TGF) and reduces glomerular filtration rate (GFR) in rats. To test this, homozygous ALMS1 knockout (KO) and littermate wild-type Dahl salt-sensitive rats were studied. TGF sensitivity was higher in ALMS1 KO rats as measured by in vivo renal micropuncture. Using confocal microscopy, we confirmed immunolabeling of ALMS1 in macula densa cells (nitric oxide synthase 1 positive), supporting a role for ALMS1 in TGF regulation. Baseline glomerular capillary pressure was higher in ALMS1 KO rats, as was mean arterial pressure. Renal interstitial hydrostatic pressure was lower in ALMS1 KO rats, which is linked to increased Na+ reabsorption and hypertension. GFR was reduced in ALMS1 KO rats. Seven-week-old ALMS1 KO rats were not proteinuric, but proteinuria was present in 18- to 22-wk-old ALMS1 KO rats. The glomerulosclerosis index was higher in 18-wk-old ALMS1 KO rats. In conclusion, ALMS1 is involved in the control of glomerular hemodynamics in part by enhancing TGF sensitivity, and this may contribute to decreased GFR. Increased TGF sensitivity, enhanced glomerular capillary pressure, and hypertension may lead to glomerular damage in ALMS1 KO rats. These are the first data supporting the role of ALMS1 in TGF and glomerular hemodynamics.NEW & NOTEWORTHY ALMS1 is a novel protein involved in regulating tubuloglomerular feedback (TGF) sensitivity, glomerular capillary pressure, and blood pressure, and its dysfunction may reduce renal function and cause glomerular damage.


Subject(s)
Alstrom Syndrome , Hypertension , Kidney Diseases , Humans , Rats , Animals , Rats, Inbred Dahl , Glomerular Filtration Rate/physiology , Hemodynamics
3.
Physiol Rep ; 11(7): e15652, 2023 04.
Article in English | MEDLINE | ID: mdl-37024297

ABSTRACT

Development of autosomal dominant polycystic kidney disease (ADPKD) involves renal epithelial cell abnormalities. Cystic fluid contains a high level of ATP that, among other effects, leads to a reduced reabsorption of electrolytes in cyst-lining cells, and thus results in cystic fluid accumulation. Earlier, we demonstrated that Pkd1RC/RC mice, a hypomorphic model of ADPKD, exhibit increased expression of pannexin-1, a membrane channel capable of ATP release. In the current study, we found that human ADPKD cystic epithelia have higher pannexin-1 abundance than normal collecting ducts. We hypothesized that inhibition of pannexin-1 function with probenecid can be used to attenuate ADPKD development. Renal function in male and female Pkd1RC/RC and control mice was monitored between 9 and 20 months of age. To test the therapeutic effects of probenecid (a uricosuric agent and a pannexin-1 blocker), osmotic minipumps were implanted in male and female Pkd1RC/RC mice, and probenecid or vehicle was administered for 42 days until 1 year of age. Probenecid treatment improved glomerular filtration rates and slowed renal cyst formation in male mice (as shown in histopathology). The mechanistic effects of probenecid on sodium reabsorption and fluid transport were tested on polarized mpkCCDcl4 cells subjected to short-circuit current measurements, and in 3D cysts grown in Matrigel. In the mpkCCDcl4 epithelial cell line, probenecid elicited higher ENaC currents and attenuated in vitro cyst formation, indicating lower sodium and less fluid retention in the cysts. Our studies open new avenues of research into targeting pannexin-1 in ADPKD pathology.


Subject(s)
Cysts , Polycystic Kidney, Autosomal Dominant , Mice , Male , Female , Humans , Animals , Polycystic Kidney, Autosomal Dominant/drug therapy , Polycystic Kidney, Autosomal Dominant/genetics , Polycystic Kidney, Autosomal Dominant/metabolism , Probenecid/pharmacology , Probenecid/metabolism , Probenecid/therapeutic use , Disease Models, Animal , Kidney/metabolism , Disease Progression , Adenosine Triphosphate/metabolism , Cysts/metabolism , Cysts/pathology , TRPP Cation Channels/genetics , TRPP Cation Channels/metabolism , TRPP Cation Channels/pharmacology
4.
Am J Physiol Renal Physiol ; 322(4): F429-F436, 2022 04 01.
Article in English | MEDLINE | ID: mdl-35224993

ABSTRACT

Obesity increases the risk of renal damage, but the mechanisms are not clear. Normally, kidneys autoregulate to keep the glomerular capillary pressure (PGC), renal blood flow, and glomerular filtration rate in a steady state. However, in obesity, higher PGC, renal blood flow, and glomerular filtration rate are noted. Together, these may lead to glomerular damage. PGC is controlled mainly by afferent arteriole resistance, which, in turn, is regulated by tubuloglomerular feedback (TGF), a vasoconstrictor mechanism. High fat-induced obesity causes renal damage, and this may be related to increased PGC. However, there are no studies as to whether high-fat diet (HFD)-induced obesity affects TGF. We hypothesized that TGF would be attenuated in obesity caused by HFD feeding (60% fat) in Sprague-Dawley rats. Sprague-Dawley rats fed a normal-fat diet (NFD; 12% fat) served as the control. We studied 4 and 16 wk of HFD feeding using in vivo renal micropuncture of individual rat nephrons. We did not observe significant differences in body weight, TGF response, and mean arterial pressure at 4 wk of HFD feeding, but after 16 wk of HFD, rats were heavier and hypertensive. The maximal TGF response was smaller in HFD-fed rats than in NFD-fed rats, indicating an attenuation of TGF in HFD-induced obesity. Baseline PGC was higher in HFD-fed rats than in NFD-fed rats and was associated with higher glomerulosclerosis. We conclude that attenuated TGF and higher PGC along with hypertension in HFD-fed obese Sprague-Dawley rats could explain the higher propensity of glomerular damage observed in obesity.NEW & NOTEWORTHY Reduced tubuloglomerular feedback, higher glomerular capillary pressure, and hypertension in combination may explain the higher glomerular damage observed in high-fat diet-induced obesity.


Subject(s)
Hypertension , Kidney Diseases , Animals , Diet, High-Fat/adverse effects , Feedback , Female , Humans , Male , Obesity/etiology , Rats , Rats, Sprague-Dawley
5.
Eur J Neurol ; 27(11): 2168-2175, 2020 11.
Article in English | MEDLINE | ID: mdl-32542878

ABSTRACT

BACKGROUND AND PURPOSE: The safety of early initiation of anticoagulant therapy in patients with ischaemic stroke related to atrial fibrillation (AF) is unknown. We investigated the safety of early initiation of direct oral anticoagulants (DOACs), vitamin K antagonists (VKAs) or no anticoagulation. METHODS: This observational, retrospective, single-centre study included consecutive patients with recent (<4 weeks) ischaemic stroke and AF. The primary outcome was the rate of major (intracranial and extracranial) bleeding in patients on different treatment schemes, i.e. DOACs, VKAs and not anticoagulated. We also investigated the rate of ischaemic cerebrovascular events and mortality. RESULTS: We included 959 consecutive patients with AF and ischaemic stroke followed up for an average of 16.1 days after the index event. A total of 559 out of 959 patients (58.3%) were anticoagulated with either VKAs (n = 259) or DOACs (n = 300). Anticoagulation was started after a mean of 7 ± 9.4 days in the DOAC group and 11.9 ± 19.7 days in the VKA group. Early initiation of any anticoagulant was not associated with an increased risk of any major bleeding [odds ratio (OR), 0.49; 95% confidence intervals (CI), 0.21-1.16] and in particular of intracranial bleeding (OR, 0.47; 95% CI, 0.17-1.29; P = 0.143) compared with no anticoagulation. In contrast to VKAs (OR, 0.78; 95% CI, 0.28-2.13), treatment with DOACs (OR, 0.32; 95% CI, 0.10-0.96) reduced the rate of major bleeding compared with no anticoagulation. Early recurrences of ischaemic stroke did not differ significantly among the three groups. CONCLUSIONS: Starting DOACs within a mean of 7 days after stroke appeared to be safe. Randomized controlled studies are needed to establish the added efficacy of starting anticoagulation early after stroke.


Subject(s)
Atrial Fibrillation , Stroke , Administration, Oral , Anticoagulants/adverse effects , Atrial Fibrillation/complications , Atrial Fibrillation/drug therapy , Brain Ischemia/complications , Brain Ischemia/drug therapy , Humans , Retrospective Studies , Stroke/complications , Stroke/drug therapy
6.
Am J Physiol Renal Physiol ; 317(6): F1649-F1655, 2019 12 01.
Article in English | MEDLINE | ID: mdl-31630543

ABSTRACT

The severity of polycystic kidney diseases (PKD) depends on the counterbalancing of genetic predisposition and environmental factors exerting permissive or protective influence on cyst development. One poorly characterized phenomenon in the cystic epithelium is abnormal purinergic signaling. Earlier experimental studies revealed the high importance of the ionotropic P2X receptors (particularly, P2X7) in the pathophysiology of the cyst wall. To study mechanisms of P2X7 involvement in cyst growth and aspects of targeting these receptors in PKD treatment we performed a CRISPR/SpCas9-mediated global knockout of the P2rx7 gene in PCK rats, a model of autosomal recessive PKD (ARPKD). A single base insertion in exon 2 of the P2rx7 gene in the renal tissues of homozygous mutant animals leads to lack of P2X7 protein that did not affect their viability or renal excretory function. However, PCK.P2rx7 rats demonstrated slower cyst growth (but not formation of new cysts) compared with heterozygous and PCK.P2rx7+ littermates. P2X7 receptors are known to activate pannexin-1, a plasma channel capable of releasing ATP, and we found here that pannexin-1 expression in the cystic epithelium is significantly higher than in nondilated tubules. P2X7 deficiency reduces renal pannexin-1 protein expression and daily urinary ATP excretion. Patch-clamp analysis revealed that lack of P2X7 increases epithelial sodium channel activity in renal tissues and restores impaired channel activity in cysts. Interpretation of our current data in the context of earlier studies strongly suggests that P2X7 contributes to cyst growth by increasing pannexin-1-dependent pathogenic ATP release into the lumen and reduction of sodium reabsorption across the cyst walls.


Subject(s)
Cysts/pathology , Kidney Diseases/pathology , Polycystic Kidney, Autosomal Recessive/metabolism , Receptors, Purinergic P2X7/metabolism , Adenosine Triphosphate/urine , Animals , CRISPR-Cas Systems , Connexins/biosynthesis , Connexins/genetics , Cysts/genetics , Epithelial Sodium Channels/metabolism , Female , Gene Knockout Techniques , Kidney Diseases/genetics , Mutagenesis, Insertional , Nerve Tissue Proteins/biosynthesis , Nerve Tissue Proteins/genetics , Polycystic Kidney, Autosomal Recessive/genetics , Pregnancy , Rats , Receptors, Purinergic P2X7/genetics , Sodium/metabolism
7.
J Immigr Minor Health ; 20(5): 1243-1260, 2018 Oct.
Article in English | MEDLINE | ID: mdl-29189993

ABSTRACT

A community needs assessment was conducted to explore barriers and facilitators to good physical and mental health among Cambodian and Latino residents in an urban community in Southern California. Thirty-six Cambodians and 29 Latinos completed the interviewer-facilitated survey administered door-to-door, and another 20 Cambodian and 18 Latino residents participated in focus groups. Crime, limited knowledge of positive health behaviors, lack of access to affordable healthcare, and lack of access to safe spaces for recreational activities were identified as threats to good health. Participant recommendations to support health in the community included increasing police presence to improve safety and reduce violence, and increasing opportunities/locations for physical exercise. While differences between Cambodian and Latino residents exist, the identified threats and suggested improvements were primarily associated with environmental factors, highlighting the need for systems level approaches that recognize the relationship between community context and health.


Subject(s)
Asian People/statistics & numerical data , Health Services Accessibility/statistics & numerical data , Health Status , Hispanic or Latino/statistics & numerical data , Mental Health/ethnology , Adult , Aged , California/epidemiology , Cambodia/ethnology , Environment , Female , Health Behavior , Health Knowledge, Attitudes, Practice/ethnology , Humans , Insurance Coverage/statistics & numerical data , Insurance, Health/statistics & numerical data , Interviews as Topic , Leisure Activities , Male , Middle Aged , Needs Assessment , Patient-Centered Care/statistics & numerical data , Public Health , Safety , Socioeconomic Factors , United States/epidemiology , Young Adult
8.
Mult Scler ; 20(14): 1912-5; discussion 1916-7, 2014 Dec.
Article in English | MEDLINE | ID: mdl-24526663

ABSTRACT

Radiologically-isolated syndrome (RIS) is a recently-defined entity, described as the incidental discovery of lesions suggestive of multiple sclerosis (MS) on brain magnetic resonance imaging (MRI) scans demonstrating dissemination in space (DIS) without symptom expression and with a normal neurological examination. Recent studies demonstrate that RIS patients present similar features of cognitive impairment as MS patients. We describe a case of a RIS patient in whom investigating cognitive functions was a useful tool for diagnostic and therapeutic decisions.


Subject(s)
Asymptomatic Diseases , Brain/pathology , Cognition Disorders/diagnosis , Incidental Findings , Multiple Sclerosis/diagnosis , Spinal Cord/pathology , Cervical Vertebrae , Cognition Disorders/psychology , Evoked Potentials, Visual , Female , Follow-Up Studies , Humans , Magnetic Resonance Imaging , Middle Aged , Multiple Sclerosis/psychology , Neuropsychological Tests , Oligoclonal Bands/cerebrospinal fluid
9.
AIDS Care ; 24(8): 1028-38, 2012.
Article in English | MEDLINE | ID: mdl-22519680

ABSTRACT

Our research aims were to: (1) assess the prevalence of two condom use problems: breakage or slippage and partial use (delayed application or early removal) among men who have sex with men (MSM) seeking services in urban US STD clinics; and (2) examine the association between these condom use problems and participant, partner and partnership characteristics. Analysis was restricted to HIV-negative MSM who reported having anal sex at least once in the preceding 3 months and who completed both the baseline and 3 month follow-up assessments. Two models were fitted using the generalized estimating equations (GEE) approach. A total of 263 MSM (median age=32 years) reported 990 partnerships. Partnerships with no condom use 422 (42.6%) were excluded. Thus, 207 MSM and 568 partnerships were included. Among condom users, 100% use was reported within 454 partnerships (79.9%) and <100% within 114 (20.1%), and 21(3.7%) reported both condom use problems, 25 (4.4%) reported only breakage, 67 (11.8%) reported only partial use, and 455 (80.1%) reported no errors. The breakage or slippage and partial use rates per condom used were 3.4% and 11.2%, respectively. A significantly higher rate of breakage or slippage occurred among non-main partnerships. Characteristics associated with increased odds for condom breakage or slippage were: lower education level (OR=2.78; CI: 1.1-7.5), non-main partner status (OR=4.1; CI: 1.5-11.7), and drunk or high during sex (OR=2.0; CI: 1.1-3.8), and for partial use: lower education level (OR=2.6; CI: 1.0-6.6), perceived partner sexually transmitted infections (STI) risk (OR=2.4; CI: 1.3-4.2), and inconsistent condom use (OR=3.7; CI: 2.0-6.6). A high percentage of MSM partnerships reported no condom use and among condom users, a sizable proportion did not use them consistently or correctly. MSM may benefit from interventions designed to increase proficiency for condom use with a particular focus on the behaviors of inconsistent and partial condom use.


Subject(s)
Condoms/statistics & numerical data , Equipment Failure/statistics & numerical data , Homosexuality, Male/statistics & numerical data , Sexual Behavior , Adult , HIV Seronegativity , Humans , Male , United States/epidemiology , Urban Health
10.
Public Health Genomics ; 14(4-5): 211-21, 2011.
Article in English | MEDLINE | ID: mdl-20051669

ABSTRACT

BACKGROUND: Family health history (FHH) is a tool used to inform individuals about inherited disease risk. Due to their disproportionate morbidity and mortality from some common chronic diseases, U.S. Latinos are an important audience for FHH information. This study examined the effects of a culturally-tailored intervention led by lay health advisors (LHAs) in delivering information about FHH on participants' intentions, self-efficacy, and conceptual knowledge. METHODS: 474 Spanish-speaking Latino participants were enrolled in the study. Individuals in the intervention group participated in a single group educational session using discussion and interactive activities to build skills for discussing FHH with one's family members and doctor, while individuals in the comparison group had a brochure read aloud to them. Pre- and post-test questionnaires were verbally administered. RESULTS: Primary dependent variables were intentions and self-efficacy to discuss FHH with family members and doctors; these increased in both groups. Multivariate analyses demonstrated that the intervention led to a significantly greater increase in self-efficacy to discuss FHH with family members (p = 0.03). LHA participants were also more than twice as likely (OR = 2.6, 95% CI = 1.3-5.0) to correctly understand the purpose of a FHH and found FHH information more useful (p < 0.0001). CONCLUSIONS: A communication intervention delivered by LHAs shows promise as an effective means of educating underserved Spanish-speaking Latinos about the importance of FHH for disease prevention. Such community-based approaches can help to close knowledge and skills gaps about FHH and increase confidence in using this information to improve the health of those most at risk.


Subject(s)
Family , Health Education/methods , Hispanic or Latino , Medical History Taking , Medically Underserved Area , Adolescent , Adult , Female , Humans , Male , Middle Aged , United States , Young Adult
11.
J Am Soc Nephrol ; 15(6): 1413-20, 2004 Jun.
Article in English | MEDLINE | ID: mdl-15153552

ABSTRACT

Reduction of renal mass by unilateral nephrectomy results in an immediate increase in renal blood flow (RBF) to the remnant kidney, followed by compensatory renal hypertrophy. Whether the increase in RBF after unilateral nephrectomy is mediated by nitric oxide (NO) was tested. It was found that immediately after nephrectomy, blood flow to the remaining kidney increased by 8% (P < 0.01), and inhibition of NO synthesis with Nomega-nitro-L-arginine methyl ester (L-NAME) blocked the increase in RBF. In addition, 2 d after nephrectomy, there was a 49% increase in RBF (corrected per gram of kidney weight), a 25% increase at 7 and 14 d, and a 16% increase after 28 d. Acute inhibition of NO synthesis with L-NAME in uninephrectomized rats caused a greater decrease in RBF on days 2 and 7 compared with controls, whereas by 14 and 28 d, the response to L-NAME was similar to controls. Urinary excretion of cyclic guanosine monophosphate, a marker for renal NO production, increased 2.5-fold by 2 d after uninephrectomy (P < 0.005) and remained at this level through 28 d. Pretreating rats chronically with a subpressor dose of L-NAME beginning 2 d before nephrectomy blocked the increase in RBF seen at 2 and 7 d and retarded the renal hypertrophy that should have developed by 7 d. It is concluded that after unilateral nephrectomy, immediate and sustained increases in RBF are mediated at least in part by NO. The hypertrophic response to unilateral nephrectomy may be partially initiated by the signal of hemodynamic changes.


Subject(s)
Kidney/pathology , Nephrectomy , Nitric Oxide/physiology , Animals , DNA/metabolism , Enzyme Inhibitors/pharmacology , Kidney/metabolism , Kidney Glomerulus/metabolism , NG-Nitroarginine Methyl Ester/pharmacology , Nitric Oxide/metabolism , Nitric Oxide Synthase/metabolism , Rats , Renal Circulation , Time Factors
12.
Hypertension ; 43(1): 79-86, 2004 Jan.
Article in English | MEDLINE | ID: mdl-14662650

ABSTRACT

We compared the phenotype of two common mouse models, C-57BL/6J (C57), which carries only the Ren-1c gene, and 129/SvJ (Sv-129), with both Ren 1d and Ren-2. We hypothesized two renin gene Sv-129 would have increased blood pressure and the renin-angiotensin system would be more influential in regulating renal function compared with one renin gene mice. Sv-129 consistently had higher blood pressure than C-57, whether conscious (128 versus 108 mm Hg, P<0.001) or anesthetized (102 versus 88 mm Hg, P<0.001). Plasma renin concentration in both conscious and anesthetized C-57 mice was 3- to 4-fold higher than in Sv-129 (P<0.05), whereas renal cortical renin content was 2.5-fold higher (P<0.005). Renal blood flow and renal vascular resistance were the same in C-57 and Sv-129. Exogenous angiotensinogen produced identical pressor and renal vasoconstrictor responses in both strains. Blocking AT1 receptors with losartan reduced blood pressure by 19 mm Hg in both strains. Nitric oxide synthase inhibition by l-NAME increased blood pressure by 29 mm Hg in C-57 and 35 mm Hg in Sv-129 mice, but the decrease in renal blood flow was 30% less in C-57 (P<0.025). We conclude that Sv-129 mice with two renin genes have higher blood pressure but lower plasma and renal renin than C-57 mice with one renin gene. Renin substrate may limit angiotensin II production in the mouse. In Sv-129, the influence of nitric oxide on renal but not systemic resistance may be exaggerated. Renin from Ren-2 may act independently of normal renin control mechanisms.


Subject(s)
Blood Pressure , Renal Circulation , Renin/genetics , Angiotensin II Type 1 Receptor Blockers , Animals , Blood Pressure/drug effects , Enzyme Inhibitors/pharmacology , Losartan/pharmacology , Male , Mice , Mice, Inbred C57BL , NG-Nitroarginine Methyl Ester/pharmacology , Nitric Oxide Synthase/antagonists & inhibitors , Phenotype , Renal Circulation/drug effects , Renin/blood
13.
Minerva Chir ; 58(6): 815-21, 2003 Dec.
Article in Italian | MEDLINE | ID: mdl-14663410

ABSTRACT

Solid pseudopapillary pancreatic tumour is an uncommon disease including 2.7% of exocrine malignancies of the pancreas. Its low incidence is associated with an uncertain prognosis and with difficult diagnostic and therapeutic problems, despite routine use of ultrasonography, TC and RMN. A case of solid pseudopapillary pancreatic tumour in a young woman is reported: the clinicopathologic features, diagnostic imaging and surgical treatment are discussed. Surgery is the primary option. Prognosis is however not fully known. From a review of the literature it is suggested that these tumours should be regarded as potentially malignant.


Subject(s)
Carcinoma, Papillary , Pancreatic Neoplasms , Adult , Carcinoma, Papillary/pathology , Carcinoma, Papillary/surgery , Female , Humans , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/surgery
14.
Am J Physiol Renal Physiol ; 282(1): F59-64, 2002 Jan.
Article in English | MEDLINE | ID: mdl-11739113

ABSTRACT

The role of endothelium-derived nitric oxide (NO) in renal baroreceptor stimulation of renin was tested comparing endothelial nitric oxide synthase (eNOS)-deficient mice with C57BL/6J (C57) controls. We measured blood pressure, renal blood flow (RBF), and plasma renin concentration (PRC) in Inactin-anesthetized mice. Blood pressure in eNOS knockout mice was higher than in controls (100 +/- 3 vs. 86 +/- 1 mmHg, respectively; P < 0.001), but RBF was similar (1.71 +/- 0.06 vs. 1.66 +/- 0.09 ml. min(-1). 100 mg kidney wt(-1), respectively), so that renal vascular resistance was also higher in the knockouts (59.81 +/- 2.07 vs. 51.81 +/- 2.66 resistance units, respectively; P < 0.025). PRC was similar (8.24 +/- 1.57 in eNOS knockouts vs. 7.10 +/- 1.19 ng ANG I. ml(-1). h(-1) in C57). NOS inhibition with nitro-L-arginine methyl ester (L-NAME) in C57 controls increased blood pressure (from 85 +/- 2 to 106 +/- 1 mmHg, P < 0.001) and decreased RBF (from 1.66 +/- 0.09 to 1.08 +/- 0.02; P < 0.005), but L-NAME had no effect in eNOS knockout mice. When renal perfusion pressure was reduced in C57 controls to 55 mmHg, PRC increased from 6.6 +/- 0.9 to 14.5 +/- 1.9 microg. ml(-1). h(-1) (P < 0.025), but this response was blocked by L-NAME. However, in eNOS knockouts, reduced renal perfusion pressure increased PRC from 7.6 +/- 1.4 to 15.0 +/- 2.8 microg. ml(-1). h(-1) (P < 0.001). Thus in the chronic absence of eNOS, blood pressure was elevated, but RBF was normal. Additionally, the absence of eNOS did not modify baroreceptor-stimulated renin, suggesting that eNOS-derived NO does not directly mediate this renin-regulating pathway.


Subject(s)
Kidney/metabolism , Nitric Oxide Synthase/genetics , Pressoreceptors/physiology , Renin/metabolism , Animals , Endothelium/physiology , Enzyme Inhibitors/pharmacology , Juxtaglomerular Apparatus/metabolism , Mice , Mice, Inbred C57BL , Mice, Knockout , NG-Nitroarginine Methyl Ester/pharmacology , Nitric Oxide/metabolism , Nitric Oxide Synthase/antagonists & inhibitors , Nitric Oxide Synthase Type II , Nitric Oxide Synthase Type III , Phenotype , Renal Circulation/physiology , Vasoconstriction/physiology
15.
Dig Dis ; 19(3): 225-31, 2001.
Article in English | MEDLINE | ID: mdl-11752841

ABSTRACT

When patients complain of problems, physicians are used to look for some physical or physiological abnormality ruling out infections, inflammatory or cancer. Unfortunately, when we talk about functional disorders we usually cannot observe any defects and it is only possible for us to know of them through the words of our patients. Developing criteria and guidelines is not an easy process, in particular for functional gastrointestinal diseases, when no disease-based biological markers exist. It is difficult to define a medical disorder in the absence of a biological "gold standard". The Rome II classification is based on the assumption that for each disorder there are symptom clusters. Symptoms have in common disturbances in sensory and/or motor gastrointestinal function, which sometimes may overlap across anatomic regions. Nevertheless, several studies provide evidence for site-specific syndromes.


Subject(s)
Colonic Diseases, Functional/therapy , Guideline Adherence , Practice Guidelines as Topic , Colonic Diseases, Functional/diagnosis , Consensus Development Conferences as Topic , Diagnosis, Differential , Humans , Severity of Illness Index
16.
Dig Liver Dis ; 33(9): 788-94, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11838615

ABSTRACT

Gastroduodenal disease associated with Helicobacter pylori infection are reviewed as well as the diagnostic approach. Generally, there are by and large two ways in which a diagnosis of infection by Helicobacter pylori can be made: by using either an invasive or non-invasive procedure. The invasive procedures involve endoscopy and biopsy Biopsy is essential since the mucosa may often appear macroscopically normal but, nevertheless, be inflamed. Once a biopsy is obtained histological examination, culture, polymerase chain reaction, detection of the presence of urease activity can be detected. The non-invasive tests that can be used to diagnose the infection are: serology, detection of labelled metabolic products of urea hydrolysis either in the breath (13CO2, 14CO2), the urine or the blood, detection of Helicobacter pylori antigen in stool specimen. At present, no single test is sufficiently reliable to definitely detect colonisation by Helicobacter pylori, and a combination of two is recommended, if feasible. Choice of the test to be used is not straightforward and relies on a series of situations, i. e., clinical setting and local expertise and availability, that the clinician must consider to obtain the best diagnostic yeld. The challenge of Helicobacter pylori eradication is not very easy to obtain. The possible scenario and the use of a new proton pump inhibitor (esomeprazole) are reviewed and discussed.


Subject(s)
Helicobacter Infections/diagnosis , Helicobacter Infections/drug therapy , Helicobacter pylori , Dyspepsia/microbiology , Gastritis/microbiology , Gastroesophageal Reflux/microbiology , Helicobacter Infections/complications , Humans , Peptic Ulcer/microbiology , Proton Pump Inhibitors , Stomach Neoplasms/microbiology
17.
Int J Pancreatol ; 17(1): 23-8, 1995 Feb.
Article in English | MEDLINE | ID: mdl-8568331

ABSTRACT

The aim of this study was to assess the incidence of fusion and duplication variants of the pancreatic duct system and their clinical significance. A total of 650 endoscopic retrograde cholangiopancreatography were reviewed; 485 cases with satisfactory imaging of the pancreatic ducts were included in the study. Anatomic variants were observed in 48 patients (9.9%), fusion variants were 54.1% of the cases (22 pancreas divisum and 4 functional divisum), and duplication variants were 45.8% (13 bifurcations of the main pancreatic duct, 4 loop, 2N-shape, 3 ring). Clinical indications to endoscopic cholangiopancreatography were idiopathic acute pancreatitis (33.3%), suspected chronic pancreatitis (18.7%), unexplained abdominal pain (14.5%), suspected pancreatic mass (10.4%), chronic hyperamylasemia (6.2%), and acute biliary pancreatitis (16.6%). Except for acute biliary pancreatitis (significantly more frequent in duplication variants), no statistical difference was observed between the groups with anatomical variants concerning clinical features.


Subject(s)
Pancreatic Ducts/anatomy & histology , Adolescent , Adult , Aged , Aged, 80 and over , Cholangiopancreatography, Endoscopic Retrograde , Female , Humans , Male , Middle Aged , Pancreatic Ducts/diagnostic imaging , Retrospective Studies
19.
Ital J Gastroenterol ; 24(7): 400-4, 1992 Sep.
Article in English | MEDLINE | ID: mdl-1392023

ABSTRACT

We have carried out a double blind placebo controlled trial to assess the effects of treatment with colloidal bismuth subcitrate in Helicobacter pylori associated non-ulcer dyspepsia. Eighty patients with dyspepsia, normal upper gastrointestinal appearances at endoscopy and H pylori associated active chronic gastritis on histology of gastric antral biopsies were included in the trial. The patients were randomised to receive colloidal bismuth subcitrate 240mg twice daily for four weeks or matching placebo and were reassessed four weeks after completing treatment. Twenty-six patients (67%) receiving colloidal bismuth subcitrate had normal histology or improved inflammation compared with five (13%) receiving placebo (p less than 0.001), and symptoms were absent or improved in 32 (82%) and two (5%) respectively (p less than 0.001). Serum IgG level was a marker of infection, and fell with successful treatment. Colloidal bismuth subcitrate is effective treatment for H pylori associated non-ulcer dyspepsia with improved gastric antral histological appearances and has a beneficial effect on symptoms.


Subject(s)
Anti-Ulcer Agents/therapeutic use , Dyspepsia/etiology , Gastritis/drug therapy , Helicobacter Infections/drug therapy , Helicobacter pylori , Organometallic Compounds/therapeutic use , Adult , Bismuth/therapeutic use , Double-Blind Method , Dyspepsia/drug therapy , Dyspepsia/pathology , Female , Gastric Mucosa/pathology , Gastritis/microbiology , Gastritis/pathology , Helicobacter Infections/complications , Helicobacter Infections/pathology , Humans , Male , Middle Aged , Prospective Studies
20.
Gut ; 31(8): 905-8, 1990 Aug.
Article in English | MEDLINE | ID: mdl-2387515

ABSTRACT

Between January 1986 and July 1988 needle knife papillotomy was attempted in 103 patients after failure of conventional access for endoscopic sphincterotomy (96 cases) or diagnostic cholangiography (seven cases). Access was obtained at the same session in 36 cases and at a subsequent attempt within 2 to 5 days in a further 43, an overall success rate of 77%. The procedure related morbidity and mortality in the therapeutic group were 5.2% and 2.0% respectively. There were no deaths or complications in the diagnostic group. Needle knife papillotomy is a valuable adjunct to conventional techniques of biliary access.


Subject(s)
Ampulla of Vater/surgery , Postoperative Complications/etiology , Aged , Female , Humans , Male , Methods
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