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BACKGROUND: Initiation of ART among people living with HIV (PLWH) having a CD4 count ≤ 350cells/µl, produces poor immunological recovery, putting them at a high risk of opportunistic infections. To mitigate this, PLWH on ART in Uganda frequently use herbal remedies like Artemisia annua and Moringa oleifera, but their clinical benefits and potential antiretroviral (ARV) interactions remain unknown. This study examined the impact of A. annua and M. oleifera on CD4 count, viral load, and potential ARV interactions among PLWH on ART at an HIV clinic in Uganda. METHODS: 282 HIV-positive participants on antiretroviral therapy (ART) with a CD4 count ≤ 350cells/µl were randomized in a double-blind clinical trial to receive daily, in addition to their routine standard of care either; 1) A. annua leaf powder, 2) A. annua plus M. oleifera, and 3) routine standard of care only. Change in the CD4 count at 12 months was our primary outcome. Secondary outcomes included changes in viral load, complete blood count, and ARV plasma levels. Participants were followed up for a year and outcomes were measured at baseline, 6 and 12 months. RESULTS: At 12 months of patient follow-up, in addition to standard of care, administration of A. annua + M. oleifera resulted in an absolute mean CD4 increment of 105.06 cells/µl, (p < 0.001), while administration of A. annua plus routine standard of care registered an absolute mean CD4 increment of 60.84 cells/µl, (p = 0.001) compared to the control group. The A. annua plus M. oleifera treatment significantly reduced viral load (p = 0.022) and increased platelet count (p = 0.025) and white blood cell counts (p = 0.003) compared to standard care alone, with no significant difference in ARV plasma levels across the groups. CONCLUSION: A combination of A. annua and M. oleifera leaf powders taken once a day together with the routine standard of care produced a significant increase in CD4 count, WBCs, platelets, and viral load suppression among individuals on ART. A. annua and M. oleifera have potential to offer an affordable alternative remedy for managing HIV infection, particularly in low-resource communities lacking ART access. TRIAL REGISTRATION: ClinicalTrials.gov NCT03366922.
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Fármacos Anti-VIH , Artemisia annua , Infecciones por VIH , Moringa oleifera , Humanos , Fármacos Anti-VIH/uso terapéutico , Antirretrovirales/uso terapéutico , Recuento de Linfocito CD4 , Hospitales , Derivación y Consulta , Uganda , Carga Viral , Método Doble CiegoRESUMEN
OBJECTIVE: To compare the efficacy of dialysate drainage between Tenckhoff (TC) catheter and Blake (BL) in peritoneal dialysis (PD) in healthy rabbits. DESIGN: Prospective experimental study. SETTING: University Teaching Hospital and University research laboratory. ANIMALS: Twenty healthy, male, New Zealand rabbits. INTERVENTIONS: PD via the TC catheter and the BL abdominal drain was compared during 3 consecutive days of dialysis delivery. MEASUREMENTS AND MAIN RESULTS: One session of PD was performed per day for 3 consecutive days (S1: first session, S2: second session, S3: third session) and each session included 4 cycles of infusion, dwell of dialysate in the abdomen, and drainage. Data collection included daily urea, creatinine, alanine aminotransferase, albumin, and potassium, in addition to hematological parameters (eg, RBC, HCT, hemoglobin, WBC, and platelet count). Statistical analysis using a mixed linear model with multiple comparisons was performed. The BL drain resulted in an increase in volume drained (ml/kg) when compared to TC catheter on S2 (third and fourth cycles) and S3 (first and second cycles). CONCLUSIONS: The BL drain proved to be superior to the TC catheter, being capable of draining a larger volume of dialysate during the drainage processes in the peritoneal PD of healthy rabbits. The TC catheter had major complications with regard to fluid retention in the abdomen, representing reduced drainage efficiency, while the BL drain showed a greater tendency for the peritoneal fluid to leak.
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Diálisis Peritoneal , Conejos , Masculino , Animales , Estudios Prospectivos , Diálisis Peritoneal/veterinaria , Soluciones para Diálisis , Cateterismo/veterinaria , CatéteresRESUMEN
Intermittent haemodialysis (IHD) is used in dogs with chronic kidney disease (CKD) to reduce azotaemia. Monitoring the cardiovascular system plays an important role in this treatment to detect cardiovascular repercussions. Heart rate variability (HRV) and dispersions of the QT interval and P wave are important markers for mortality risk in humans. This study aimed to describe the time-domain and frequency-domain heart rate variability indexes, P and QT dispersions and electrocardiographic alterations observed in dogs with Stage IV CKD undergoing IHD. Thirty dogs of both sexes, of varying ages and breeds, and weighing between 15 and 30 kg were used. Animals were divided into three groups, control (10 healthy dogs), clinical treatment (10 dogs with CKD IV submitted to clinical treatment twice a week) and IHD (10 dogs with CKD IV submitted to clinical treatment and to dialysis treatment with intermittent haemodialysis twice a week). Clinical, laboratory, HRV indexes and electrocardiographic parameters, as well as QT and P-wave dispersions, were assessed in both CKD groups, prior to and after the end of each clinical treatment/IHD session during the first three sessions. Dogs with CKD IV undergoing IHD had clinically important electrolyte imbalances, primarily hypokalaemia, and pertinent electrocardiographic findings, such as the occurrence of supraventricular arrhythmias and increases in possible predictive parameters for arrhythmias. In spite of these observations, HRV indexes were better in animals undergoing haemodialysis and, in addition, IHD was more effective at reducing levels of creatinine, urea and phosphorus compared to intravenous fluid therapy treatment.
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Patients with chronic kidney disease (CKD) have paradoxical hemostatic potential because they have bleeding episodes but are also prone to thrombosis. Few studies have evaluated blood viscoelastic properties in dogs with kidney disease; on the other hand, hypercoagulability has been observed in these patients. It is also emphasized that the platelet function and its participation in this process have not yet been fully understood. The objective of this study was to evaluate and compare the Thrombin Generation Test (TGT) and also viscoelastic properties of the blood measured by thromboelastometry (TEM) in dogs with proteinuria in CKD. Twenty healthy dogs (Control Group) and 19 dogs with CKD in stage III or IV, classified according to International Renal Interest Society - IRIS, were selected, and the reference test of urine protein:creatinine ratio (UPCR) should be greater than one (CKD group). Blood samples for TEM, thrombin generation, Prothrombin Time (PT), activated Partial Thromboplastin Time (aPTT), and fibrinogen concentration was collected at a single time for both groups after inclusion criteria being confirmed. Statistical analysis was performed according to the distribution of variables at 5% significance level. Differences were observed between healthy dogs and those with proteinuria in CKD noted in TEM. The TGT was unable to differentiate between sick and healthy groups. However, when the nephropathy was stratified, increases in TTP and peak thrombin concentration by TGT were observed in females and dogs over 30 days of diagnosis of CKD. Both tests signaled a discrete state of hypercoagulability. In fact, TEM is more sensitive to detect hypercoagulability in dogs with CKD. However, the TGT has potential clinical application by allowing long-term sample storage.(AU)
Os pacientes com doença renal crônica (DRC) apresentam um potencial hemostático paradoxal, pois apresentam episódios de sangramento, mas também são propensos à trombose. Poucos estudos avaliaram as propriedades viscoelásticas sanguíneas em cães com doenças renais, entretanto, a hipercoagulabilidade já foi observada nestes pacientes. Ressalta-se ainda que a função plaquetária e sua participação neste processo ainda não foram totalmente esclarecidas. O objetivo foi avaliar e comparar o teste de geração de trombina (TGT) e as propriedades viscoelásticas sanguíneas medidas pela tromboelastometria (TEM) em cães com DRC proteinúrica. Foram selecionados 20 cães saudáveis (grupo controle) e 19 cães com DRC em estágios III ou IV classificados segundo o IRIS e a relação proteína/creatinina urinária maior que um (grupo DRC). As amostras de sangue para a realização da tromboelastometria (TEM), geração de trombina, tempo de protrombina (TP), tempo de tromboplastina parcial ativada (TTPA) e concentração de fibrinogênio foram colhidas em momento único para ambos os grupos após os critérios de inclusão confirmados. A análise estatística foi realizada de acordo com a distribuição das variáveis, ao nível de 5% de significância. Foi observada diferença entre os cães saudáveis e os com DRC proteinúrica observados na TEM. O teste de geração de trombina não foi capaz de diferenciar os grupos doente e saudável. Entretanto, quando os nefropatas foram analisados de forma estratificada, foram observados aumentos do ETP e da concentração máxima de trombina (peak) pelo TGT em fêmeas e em cães com mais de 30 dias de diagnóstico da DRC. Ambos os testes sinalizando para um discreto estado de hipercoagulabiliade. A tromboelastometria é mais sensível para detectar a hipercoagulabilidade em cães com DRC. Entretanto, o teste de geração de trombina tem melhor aplicabilidade por permitir o armazenamento da amostra em longo prazo.(AU)
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Animales , Perros , Trombosis/prevención & control , Trombina , Insuficiencia Renal Crónica/sangre , Insuficiencia Renal Crónica/veterinaria , Hemorragia/prevención & control , Hemorragia/veterinaria , Hemostasis , Proteinuria/veterinaria , Tromboelastografía/veterinariaRESUMEN
In our perinatal unit we applied the ten steps of WHO/UNICEF for Baby Friendly Hospital Initiative and evaluated the percentage of exclusive (EBF) or complementary breastfeeding (CBF), and of formula fed (FF) healthy full-term infants (HFI) at hospital discharge (HD). HFI performing EBF at HD were 85.3%, a quite high value. At the age of 3 mths EBF percentage ranged between 59-62.4%, and at 6 mths it decreased to 51.7-37.7%. Customer satisfaction questionnaire at HD ranked "good" to "very good" in 92.8%. Causes of breastfeeding reduction with time and comparison with previous and actual situation in Italy and civilized countries are discussed.
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Lactancia Materna , Femenino , Humanos , Recién Nacido , Embarazo , VacunaciónRESUMEN
Modern drug therapy of epilepsy is complicated by the inability of drugs to control seizures in some patients and side effects that range in severity from minimal impairment of the central nervous system to death from aplastic anemia or hepatic failure. Medicinal plants used in traditional medicine for the treatment of epilepsy have been scientifically shown to possess promising anticonvulsant activities in animal models for screening for anticonvulsant activity and can be a source of newer anticonvulsants. The aim of this study was to investigate the preliminary phytochemical properties, anticonvulsant and anxiolytic activities of Melanthera scandens aqueous and ethanolic extracts. Phytochemicals from the aqueous and ethanolic extracts were screened by standard methods. Anticonvulsant activity was evaluated against pentylenetetrazol (PTZ)-induced seizure model in rats. The effect of the extract at oral dose levels of 250, 500 and 1000 mg/kg was evaluated in an experimental rat model, using diazepam (5 mg/kg) as positive control. Anxiolytic activity was performed using elevated plus maze method. Phytochemical screening revealed that M. scandens extracts contain carbohydrates, flavonoids, saponins, glycosides, tannins, terpenoids, phenols and phytosterols. The aqueous extract at a dose of 500 mg/kg significantly increased seizure latency (P=0.0023), while the ethanolic extract did not have a significant effect on seizure latency. Both extracts significantly reduced the seizure severity (P= 0.0155), and provided up to 100% protection against PTZ induced death at 1000 mg/kg. Both extracts had no significant effect on the duration of PTZ induced seizures. Both extracts were found to increase the number of entries and the time spent in the open arms of the maze at a dose of 250 mg/kg, indicating anxiolytic activity, which was not seen at higher doses (500 and 1000 mg/kg). The total numbers of entries into the closed arm were significantly reduced at 500 and 1000 mg/kg oral doses of both extracts, indicating a reduction in locomotor activity of the rats. The results obtained in this study suggest that both the aqueous and ethanolic extracts of M. scandens possess anticonvulsant and anxiolytic activities in a rat model.
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Este trabalho teve como objetivo determinar a ocorrência e os fatores de risco associados à infecção por Corynebacterium pseudotuberculosis em caprinos e ovinos do semiárido da Paraiba. De 640 animais examinados, 7,7% (49/640) apresentavam evidências clínicas de linfadenite caseosa. Em 59,2% (29/49) destes animais havia apenas as cicatrizes de abscessos anteriormente rompidos; em 40,8% (20/49) dos animais, os abscessos estavam intactos. Desses 20 animais, 13 (65%) caprinos apresentaram 14 abscessos, enquanto que sete (35%) ovinos apresentaram oito abscessos. Em ambas as espécies, o linfonodo pré-escapular foi o mais acometido. No exame microbiológico, constatou-se que C. pseudotuberculosis foi o agente mais frequentemente isolado, em 15 (68,2%) amostras; em uma (4,5%) foi isolado Staphylococcus coagulase negativa; uma (4,5%) Enterococcus sp.; uma (4,5%) o Proteus mirabilis e Pseudomonas aeruginosa; e em quatro (18,2%) amostras não houve crescimento bacteriano. O modelo final de regressão logística mostrou que animais provenientes de rebanhos em que seus proprietários deixavam os abscessos romperem naturalmente tiveram maior chance de apresentar linfadenite caseosa (odds ratio =8,19; IC 95% =1,75-38,25; p=0,008). Conclui-se que os caprinovinocultores da região devem adotar medidas profiláticas em seus rebanhos, como abertura e drenagem precoce dos abscessos superficiais e destino adequado do conteúdo. Tais medidas, associadas à inspeção periódica do rebanho, descarte de animais doentes e não introdução de animais infectados, contribuirão significativamente para o controle desta infecção.
This study aimed to determine the occurrence and risk factors associated with Cory nebacterium pseudotuberculosis infection in goats and sheep in semiarid region of Paraiba State, Northeastern Brazil. Of the 640 animals examined, 7.7% (49/640) had clinical evidence of caseous lymphadenitis. In 59.2% (29/49) of these animals there was only the scars of previously ruptured abscesses and in 40.8% (20/49) of the animals abscesses were intact. Of these 20 animals 13 (65%) goats had 14 abscesses, whereas seven (35%) sheep had eight abscesses. In both species, pre-scapular lymph node was the most involved. C. pseudotuberculosis was the agent most frequently isolated, in 15 (68.2%) samples, and in one (4.5%) coagulase-negative Staphylococcus was isolated, one (4.5%) Enterococ cus sp., one (4.5%) Proteus mirabilis and Pseudomonas aeruginosa, and in four (18.2%) samples there was no bacterial growth. The final logistic regression model showed that animals from herds where their owners let the abscesses break naturally presented larger odds of caseous lymphadenitis (odds ratio = 8.19, 95% CI = 1.75 - 38.25, p = 0.008). We conclude that goat/sheep owners of the region should adopt preventive measures in their herds, such as early opening and drainage of superficial abscesses, and appropriate destination of the content. Such measures, in addition to regular inspection of the flock, disposal of diseased animals and introduction of non-infected animals will contribute to the control of this infection.
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Animales , Corynebacterium pseudotuberculosis/patogenicidad , Linfadenitis/veterinaria , Ovinos/microbiología , Brotes de Enfermedades/veterinaria , /prevención & control , Prevención de Enfermedades , Factores de RiesgoRESUMEN
AIM: Endoscopic variceal ligation (EVL) is recommended for the treatment of esophageal variceal bleeding. The aim of this study was to assess the most cost-effective timing of endoscopic follow-up after variceal eradication. METHODS: Cirrhotics with esophageal varices treated between January 2008 and January 2009 until reached variceal obliteration were retrospectively analyzed for technical aspects and for outcomes. RESULTS: Out of 127 patients treated with EVL, 103 were included. Number of sessions to achieve variceal obliteration and number of bands for each session were 2.8±1.3 (range 1-7) and 4.6±1 (range 2-7), respectively. The placement of >5 bands per session was not associated with higher incidence of complications (19.6% vs. 17.8%, P=ns). Esophageal ulcers were observed in 42% of patients when the interbanding interval was <20 days (versus 15% for interval >20 days, P<0.05). Once obliteration was achieved, varices reappeared in 28% of patients; the early appearance of small varices was not associated with bleeding. CONCLUSION: A longer interbanding interval reduces the incidence of procedural-related complications. After variceal obliteration an early endoscopic control is not useful because it does not influence the approach and does not change the patient outcome.
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Várices Esofágicas y Gástricas/cirugía , Esofagoscopía , Hemorragia Gastrointestinal/cirugía , Cirrosis Hepática/complicaciones , Várices Esofágicas y Gástricas/complicaciones , Várices Esofágicas y Gástricas/etiología , Esofagoscopía/métodos , Hemorragia Gastrointestinal/etiología , Humanos , Ligadura/métodos , Recurrencia , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Over the past fifteen years, numerous observations have linked Helicobacter pylori (H. pylori) infection to ischemic heart disease (IHD). Despite the controversial literature data, it has been postulated that if a role is plausible, it will be in the early events of the acute coronary syndrome. According to this model, we focused on the potential pathogenic mechanisms relating H. pylori to IHD like platelet aggregation and thrombosis. To identify all publications in this field, a MEDLINE search of studies published in English from 1965 to 2009 was conducted. Although very few investigations were found, these showed data of paramount importance. In particular, it has been demonstrated that some strains of H. pylori bind von Willebrand factor and interact with glycoprotein Ib to induce platelet aggregation in humans. In experiments from animal models, such infection promoted the formation of platelet aggregates by both a marked increase in the flux of rolling leukocytes and the appearance of platelet and leukocyte-platelet aggregates in gastric venules. This aggregate formation was abrogated by antibodies against specific adhesion molecules (L- and P-selectin). The future challenge is to gain more knowledge in this field and to translate these information into clinical practice.
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Infecciones por Helicobacter/complicaciones , Helicobacter pylori/patogenicidad , Isquemia Miocárdica/microbiología , Trombosis/microbiología , Enfermedad de la Arteria Coronaria/microbiología , Humanos , Infarto del Miocardio/microbiología , Agregación Plaquetaria/fisiología , Factores de RiesgoRESUMEN
Neutral endopeptidase degrades atrial natriuretic peptide (ANP) and bradykinin and may generate endothelin-1 from big-endothelin. In advanced cirrhosis, sodium retention is accompanied by elevated plasma ANP levels, and infusion of ANP causes hypotension, but in normal humans increasing the concentration of ANP through the inhibition of neutral endopeptidase, localized in renal proximal tubule cells, causes natriuresis without any arterial pressure drop. The purpose of this study was the assessment of kidney neutral endopeptidase expression and responses to candoxatrilat (a specific inhibitor of this enzyme) in rats with CCl4-induced cirrhosis. Two groups of control rats (n = 5) were injected with vehicle or 3 mg/kg candoxatrilat. Three groups of cirrhotic rats with ascites (n = 10) received vehicle alone or 3 or 10 mg/kg candoxatrilat. In cirrhotic rats, Western blot analysis revealed a 170% increase in renal neutral endopeptidase protein content (P < 0.03), mainly in the proximal nephron and macula densa, and both candoxatrilat dosages increased plasma ANP levels, urinary volume, and urinary excretion of sodium, ANP, and cGMP compared with vehicle alone (all P < 0.03). Candoxatrilat (10 mg/kg) also reduced tubular solute-free water reabsorption (P < 0.03) in cirrhotic rats, but renal blood flow, arterial pressure, and plasma renin activity were unaffected. Neutral endopeptidase inhibition has natriuretic and aquaretic actions in cirrhosis without any effect on blood pressure and kidney perfusion due to a significant overexpression of this enzyme in renal cortex.
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Riñón/enzimología , Riñón/fisiopatología , Cirrosis Hepática/enzimología , Neprilisina/análisis , Animales , Western Blotting , Tetracloruro de Carbono , Ácidos Ciclohexanocarboxílicos/farmacología , Diuresis , Inhibidores Enzimáticos/farmacología , Cirrosis Hepática/inducido químicamente , Cirrosis Hepática/fisiopatología , Masculino , Natriuresis , Neprilisina/antagonistas & inhibidores , Concentración Osmolar , Ratas , Ratas WistarRESUMEN
BACKGROUND AND AIM: In preascitic cirrhosis increased sodium retention occurs in kidney distal tubule in spite of normal aldosterone plasma levels. No clearance technique can dissect the respective contribution to sodium retention exerted by Henle's loop, distal convoluted tubule and collecting duct, so we evaluated proximal and distal tubular sodium handling in preascites during two manoeuvres that temporarily increase aldosterone secretion. METHODS: Ten patients with compensated cirrhosis and nine controls were studied in recumbency, during standing and after dopamine receptor blockade with metoclopramide through: 4 h renal clearances of sodium, potassium, lithium and creatinine; plasma levels of active renin and aldosterone. RESULTS: Whilst comparable in recumbency, aldosterone levels significantly rose during standing and after metoclopramide in both groups. In patients, dopaminergic blockade caused a fall of distal sodium delivery (P < 0.01) but urinary sodium excretion was unchanged because the reabsorbed fraction of distal sodium delivery also fell (P < 0.03). Cirrhotic patients showed the same findings in the passage from recumbency to standing. CONCLUSIONS: In preascitic cirrhosis, the distal tubular segments of the nephron are able to cope with decreases in tubular flow by reducing reabsorption at an aldosterone-independent site (possibly the loop of Henle).
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Aldosterona/fisiología , Túbulos Renales Distales/metabolismo , Cirrosis Hepática/metabolismo , Sodio/metabolismo , Adulto , Anciano , Aldosterona/sangre , Antagonistas de Dopamina/farmacología , Femenino , Humanos , Riñón/fisiopatología , Túbulos Renales Distales/efectos de los fármacos , Litio/metabolismo , Cirrosis Hepática/fisiopatología , Masculino , Metoclopramida/farmacología , Persona de Mediana Edad , Natriuresis/efectos de los fármacos , Postura , Renina/sangre , Posición SupinaRESUMEN
Respiratory bronchiolitis associated with interstitial lung disease (RB-ILD), first described by Niewoehner et al in an autopsy study of cigarette smokers who died from non pulmonary causes in 1974, is a rare entity that should be distinguished from the other interstitial lung diseases and in particular from desquamative interstitial pneumonia, although the two conditions share a similar histopathological pattern. RB-ILD is clearly connected with tobacco smoking and has been inserted in the "smoking related interstitial lung diseases" together with DIP and Cell histiocytosis of Langerhans; it may also be associated with occupational exposure to machine fumes. The following is a case report of a patient with both smoking and occupational exposure.
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Bronquiolitis/complicaciones , Enfermedades Pulmonares Intersticiales/complicaciones , Fumar/efectos adversos , Bronquiolitis/diagnóstico , Bronquiolitis/patología , Diagnóstico Diferencial , Humanos , Enfermedades Pulmonares Intersticiales/diagnóstico , Enfermedades Pulmonares Intersticiales/patología , Masculino , Persona de Mediana Edad , Pronóstico , Pruebas de Función RespiratoriaRESUMEN
BACKGROUND AND AIMS: Patients with preascitic liver cirrhosis display significant renal sodium retention in the upright posture and an exaggerated natriuresis during recumbency. To date, intrarenal sodium handling in these patients has not been studied using lithium clearance and fractional excretion techniques during recumbency and orthostatism. METHODS: Ten patients with preascitic (Child-Pugh A) liver cirrhosis and 10 healthy subjects underwent the following measurements during recumbency and then after four hours of standing: (a) active renin and aldosterone plasma levels; and (b) renal clearance of creatinine, sodium, potassium, and lithium (an index of fluid delivery to the loop of Henle). RESULTS: Unlike the control group, in the upright posture patients had significantly lower values of lithium clearance and fractional excretion compared with recumbency (21.6 (8.6) v 30.5 (10.2) ml/min (p<0.03) and 12.8 (4.4)% v 20.8 (4.9)% (p<0.01), respectively). Our patients showed maintenance of the glomerular-tubular balance-that is, the correlation between creatinine clearance and proximal tubular reabsorption of fluid-during both recumbency and in the upright posture (r=0.96, p<0.001; r=0.97, p<0.001, respectively). In contrast, patients displayed tubuloglomerular feedback only in the supine position. This was demonstrated by the observation of a negative correlation between lithium fractional excretion (a measure of the fractional delivery of sodium to the distal nephron) and filtered sodium load only in recumbency (r=-0.73; p< 0.03) and not during standing (r=0.22; p> 0.05). CONCLUSIONS: This study suggests that both the reduction in fluid and sodium delivery to the distal nephron and loss of tubuloglomerular feedback (the mechanism increasing glomerular filtration rate when the distal tubule is reached by a reduced sodium load) contribute towards the tendency to sodium retention in compensated cirrhosis during prolonged upright posture.
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Riñón/metabolismo , Litio/farmacocinética , Cirrosis Hepática/metabolismo , Postura , Adulto , Aldosterona/sangre , Estudios de Casos y Controles , Creatinina/sangre , Femenino , Humanos , Glomérulos Renales/metabolismo , Túbulos Renales/metabolismo , Masculino , Tasa de Depuración Metabólica , Persona de Mediana Edad , Renina/sangre , Sodio/sangre , Estadísticas no ParamétricasRESUMEN
OBJECTIVES: Several studies in human cirrhosis have demonstrated increased nitric oxide (NO) production. In experimental animals, intracerebroventricular administration of NO donors causes a marked depression of the endogenous dopaminergic activity, a function known to be physiologically recruited and exerting a natriuretic function in patients with compensated cirrhosis. The aim of this study is to evaluate the interaction between the systemic plasma levels of NO, the endogenous dopaminergic activity and the main parameters of renal function in patients with liver cirrhosis of differing degrees of severity. METHODS: A total of 21 patients (11 with preascitic and 10 with nonazotemic diuretic-free ascitic cirrhosis) and 10 healthy control subjects underwent the following tests: a) basal plasma renin activity (PRA) and aldosterone levels; b) renal clearances of sodium, potassium, inulin, para-minohippurate and lithium (the latter being a measure of the fluid delivery to the distal nephron); c) NO systemic plasma levels measured through paramagnetic resonance spectroscopy as nitrosylhemoglobin complexes; d) endogenous dopaminergic activity, evaluated by means of the incremental prolactin and aldosterone plasma levels after dopaminergic blockade with i.v. metoclopramide. RESULTS: NO plasma values and endogenous dopaminergic activity, although significantly increased with respect to healthy controls, were not different in the two groups of patients. The plasma NO/PRA ratio was significantly higher in the group of compensated patients with respect to ascitic cirrhotics (respectively, 18.3 +/- 11.8 vs 3.5 +/- 2.6 A.U./ng/ml/h, p < 0.001). Compared with compensated cirrhotics, patients with ascites showed significantly lower values of glomerular filtration rate (GFR) and renal plasma flow (RPF). Interestingly, GFR values were substantially the same in the ascitic patients and the control subjects. Compensated patients displayed a significant positive correlation between metoclopramide-induced incremental aldosterone plasma levels (i.e., endogenous dopaminergic tone) and fractional excretion of sodium (r = 0.58; p < 0.05). In the group of compensated patients, NO levels correlated inversely with creatinine plasma concentrations (r = -0.85; p < 0.001) and directly with inulin clearance (r = 0.65; p < 0.05). CONCLUSIONS: These data show that, at least in compensated cirrhotic patients, the stimulation of systemic NO production and the increased dopaminergic function may be mechanisms preventing renal perfusion, GFR, and fractional excretion of sodium from precocious reductions.
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Riñón/fisiopatología , Cirrosis Hepática/sangre , Cirrosis Hepática/fisiopatología , Óxido Nítrico/sangre , Receptores Dopaminérgicos/fisiología , Uremia/sangre , Uremia/fisiopatología , Vasodilatadores/sangre , Adulto , Femenino , Humanos , Túbulos Renales/fisiopatología , Cirrosis Hepática/complicaciones , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Uremia/complicacionesRESUMEN
BACKGROUND: Asbestos exposure has been definitively found to be associated with both mesothelioma and lung cancer. Nevertheless, in the overall population of oil refinery workers potentially exposed to asbestos, many studies clearly show a definitely increased risk of mesothelioma, but no proven excess of lung cancer after comparison to the general population. Through the presentation of new data and the re-appraisal of two recent and independent epidemiological studies conducted in Liguria, Italy, and Ontario, Canada, we attempt to shed light on this apparently paradoxical finding. METHODS: Lung cancer mortality was studied among maintenance workers exposed to asbestos, and among two other subgroups of refinery employees: blue collar and white collar workers. The comparison with blue collar workers was performed in order to take into account the role of healthy worker effect, smoking habit, and the socioeconomic level. The comparison with white collar workers was performed to control for other occupational lung carcinogens. RESULTS AND CONCLUSIONS: Results reveal a consistency between the two studies and show that 96-100% of the mesotheliomas and 42-49% of the lung tumors arising among maintenance workers were attributable to asbestos exposure. Our new analysis, estimating two cases of asbestos-related lung cancer for each case of mesothelioma, confirms published findings on the magnitude of asbestos-related tumors in oil refineries.
Asunto(s)
Amianto/efectos adversos , Neoplasias Pulmonares/inducido químicamente , Mesotelioma/inducido químicamente , Exposición Profesional , Petróleo/efectos adversos , Interpretación Estadística de Datos , Femenino , Humanos , Italia/epidemiología , Neoplasias Pulmonares/epidemiología , Masculino , Mesotelioma/epidemiología , Enfermedades Profesionales/mortalidad , Neoplasias Pleurales/inducido químicamente , Neoplasias Pleurales/epidemiología , Fumar/efectos adversosRESUMEN
Lymphotactin (Lptn) is a new protein belonging to the C or gamma subfamily of chemokines with only two of the four cysteine residues. Lptn was reported to act specifically on T lymphocytes and not on monocytes and neutrophils. To understand better the spectrum of action of Lptn we have examined its ability to induce natural killer (NK) cell migration. Freshly isolated human NK cells as well as long-term cultured NK cells propagated in interleukin-2 (IL-2)-containing medium migrated in response to Lptn. Optimal activity was observed at concentrations ranging from 50 to 200 ng/ml, and the efficacy was comparable to that of MCP-1, the prototype of C-C chemokines. Migration in response to Lptn was chemotaxis rather than chemokinesis as determined in a checkerboard analysis. Migration of NK cells was comparable to that observed with T lymphocytes from the same donor, under the same experimental conditions. Finally, in contrast to other cytokines (IL-2 and IL-12) which in addition to chemotaxis augment NK cell adhesion to endothelial cells in vitro, Lptn did not affect the adhesiveness of NK cells to vascular endothelium.