Volcanic Vortex Rings: Axial Dynamics, Acoustic Features, and Their Link to Vent Diameter and Supersonic Jet Flow.

By injecting a mixture of gas and pyroclasts into the atmosphere, explosive volcanic eruptions frequently generate vortex rings, which are toroidal vortices formed by the jet's initial momentum. Here, we report high-speed imaging and acoustic measurements of vortex rings sourcing from gas-rich eruptive jets at Stromboli volcano (Italy). Volcanic vortex rings (VVRs) form at the vent together with an initial compression acoustic wave, VVRs maximum rise velocity being directly proportional to the amplitude and inversely proportional to the duration of the compression wave. The axial rise and acoustic signature of VVRs match well those predicted by recent fluid-dynamic experiments. This good match allows using the high-frequency (80-1,000 Hz) component of the jet sound and the time-dependent rise of VVRs to retrieve two key eruption parameters: the Mach number of the eruptive jets (<1.5) and vent diameter (∼0.7 m), respectively, the latter being confirmed independently by direct Uncrewed Aerial Vehicle observations.

Anticoagulación en enfermedad tromboembólica venosa / Anticoagulant therapy in venous thromboembolic disease

INTRODUCCIÓN: La enfermedad tromboembólica venosa está comprendida por la trombosis venosa profunda y el tromboembolismo pulmonar, las cuales son enfermedades comunes con alta morbilidad y mortalidad, incluso antes del diagnóstico. El tratamiento está basado principalmente en la terapia anticoagulante, con diferentes opciones dependiendo del ámbito clínico y la estabilidad del paciente (terapia oral vs parenteral). Objetivo: Revisar las diferentes opciones y escenarios clínicos para la indicación de terapia anticoagulante, basados en la evidencia médica actual. Metodología: Se realizó una búsqueda sistemática en las bases de datos PubMed, Scopus, Google Académico y Scielo sobre estudios que evaluaran la indicación de la terapia anticoagulante en pacientes con diagnóstico de enfermedad tromboembólica venosa, principalmente, estudios aleatorizados controlados y metaanálisis. Discusión y Resultados: Fueron encontrados estudios aleatorizados controlados donde se evidencian menores tasas de sangrado y recurrencia de la enfermedad tromboembólica venosa a favor de los anticoagulantes directos, excluyendo algunas situaciones especiales como cáncer y enfermedad renal crónica avanzada. Conclusión: La terapia anticoagulante es el pilar del tratamiento en la enfermedad tromboembólica, disminuyendo la morbilidad y mortalidad de esta entidad, aunque aumenta el riesgo de sangrado. Anteriormente, los anticoagulantes antagonistas de la vitamina K eran la única opción terapéutica, pero con altas tasas de sangrado, afortunadamente desde hace algunos años contamos con los anticoagulantes directos con mejores perfiles de seguridad y menor tasa de sangrado.

ABSTRACTS: Venous thromboembolic disease includes deep venous thrombosis and pulmonary embolism, which are common diseases with high morbidity and mortality. The treatment is based mainly on anticoagulant therapy, with different options depending on clinic context and patient stability (oral vs parenteral therapy). Objective: To review evidence based medical information regarding the use of anticoagulant therapy in venous thromboembolism. Methods: We performed a systematic review of PubMed, Scopus, Google scholar and Scielo databases, of randomized controlled studies and meta-analysis evaluating anticoagulant therapy in patients with thromboembolic venous disease. Results: Except for tromboembolic disease in patients with cancer or chronic kidney disease anticoagulation with direct (new) oral agents led to less bleeding episodes and lower relapse rate. Conclusion: anticoagulant therapy is the basis of treatment for thromboembolic disease, decreasing morbidity and mortality. New oral anticoagulants' are associated to better clinical results, notwithstanding a slight increase in bleeding episodes.

Necrotizing fasciitis following measles vaccine administration: a case report.

BACKGROUND: The occurrence of adverse events following immunization (AEFI) in national immunization programmes is very rare; however, if they occur causality assessment is conducted to identify the associated cause. In the report, we describe a case of severe necrotizing fasciitis in the left arm of a 9-month old boy following administration of the measles vaccine. CASE PRESENTATION: A 9-month old boy presented with swelling on the left upper arm and adjoining the chest area, low-grade continuous fever, frequent passage of loose watery stool and persistent cries 24 h after measles vaccine was administered on the left upper arm. On examination, he was mildly pale, febrile, anicteric. Extensive erythema of the left upper arm occurred thereafter with extensive scalded skin lesions involving the deltoid area, the upper chest wall and arm. This was followed by desquamation of the affected areas and severe necrosis. A diagnosis of severe necrotizing fasciitis was made. A causality assessment was conducted by the state AEFI committee using the detailed AEFI investigation forms to identify the cause of the incidence. CONCLUSION: Here we present a rare case of necrotizing fasciitis which could have been caused by incorrect use of reconstituted measles vaccine. Hence we recommend training of routine immunization service providers on proper vaccine management as well as intensified supervision of immunization sessions.

Experimental simulations of volcanic ash resuspension by wind under the effects of atmospheric humidity.

Ash deposited during volcanic eruptions can be resuspended by wind and become hazardous for health and infrastructure hours to decades after an eruption. Accurate resuspension forecasting requires accurate modelling of the threshold friction velocity of the volcanic particles (Uth*), which is the key parameter controlling volcanic ash detachment by wind. Using an environmental wind tunnel facility this study provides much needed experimental data on volcanic particle resuspension, with the first systematic parameterization of Uth* for ash from the regions Campi Flegrei in Italy and also Eyjafjallajökull in Iceland. In this study atmospheric relative humidity (and related ash moisture content) was systematically varied, from <10% to >90%, which in the case of the Eyjafjallajökull fine ash (<63 µm) produced a twofold increase in Uth*. Using the Campi Flegrei fine ash (<63 µm) an increase in Uth* of only around a factor of 1.5 was observed. Reasonable agreement with force balance resuspension models was seen, which implied an increase in interparticle adhesion force of up to a factor of six due to high humidity. Our results imply that, contrary to dry conditions, one single modelling scheme may not satisfy the resuspension of volcanic ash from different eruptions under wet conditions.

Patient-derived solitary fibrous tumour xenografts predict high sensitivity to doxorubicin/dacarbazine combination confirmed in the clinic and highlight the potential effectiveness of trabectedin or eribulin against this tumour.

BACKGROUND: Preclinical models that mimic pathological and molecular features of solitary fibrous tumour (SFT) represent an important tool to select effective regimes and novel compounds to be tested in the clinic. This study was aimed at developing two preclinical models of SFT, assessing their predictive value in the clinic and selecting potential novel effective treatments. MATERIAL AND METHODS: Two dedifferentiated-SFT (D-SFT) models obtained from patients' biopsies were grown in immunodeficient mice. The antitumour activity on these models of doxorubicin, dacarbazine (DTIC), ifosfamide (monotherapy or combination), trabectedin and eribulin was tested. Twelve SFT patients were treated with doxorubicin and DTIC. Response by RECIST, progression-free survival and overall survival were retrospectively evaluated, distinguishing malignant-SFT (M-SFT) and D-SFT. RESULTS: Two D-SFT patient-derived xenografts (PDXs) that represent the first available preclinical in vivo models of SFT were developed and characterised. Doxorubicin/DTIC, DTIC/ifosfamide, doxorubicin/ifosfamide combinations consistently induced better antitumour activity than the single-agents. Particularly, doxorubicin/DTIC combination caused a max tumour volume inhibition >80% in both models. Doxorubicin/DTIC combo showed activity also in the case-series. Best RECIST responses were: 6 responses (M-SFT = 2 of 7, D-SFT = 4 of 5), 1 stable disease, 5 progressions, with a 6-month median progression-free survival (M-SFT = 6, D-SFT = 10 months). The PDXs were very sensitive to trabectedin and eribulin. CONCLUSION: Doxorubicin plus DTIC combination was effective in our two D-SFT mice models and appeared to be active also in the clinic, especially in high-grade D-SFT patients. Among additional drugs tested in the PDXs, trabectedin and eribulin were highly effective, providing a rational to test these drugs in D-SFT patients.

Inducible ablation of dopamine D2 receptors in adult mice impairs locomotion, motor skill learning and leads to severe parkinsonism.

Motor execution and planning are tightly regulated by dopamine D1 and D2 receptors present in basal ganglia circuits. Although stimulation of D1 receptors is known to enhance motor function, the global effect of D2 receptor (D2R) stimulation or blockade remains highly controversial, with studies showing increasing, decreasing or no changes in motor activity. Moreover, pharmacological and genetic attempts to block or eliminate D2R have led to controversial results that questioned the importance of D2R in motor function. In this study, we generated an inducible Drd2 null-allele mouse strain that circumvented developmental compensations found in constitutive Drd2-/- mice and allowed us to directly evaluate the participation of D2R in spontaneous locomotor activity and motor learning. We have found that loss of D2R during adulthood causes severe motor impairments, including hypolocomotion, deficits in motor coordination, impaired learning of new motor routines and spontaneous catatonia. Moreover, severe motor impairment, resting tremor and abnormal gait and posture, phenotypes reminiscent of Parkinson's disease, were evident when the mutation was induced in aged mice. Altogether, the conditional Drd2 knockout model studied here revealed the overall fundamental contribution of D2R in motor functions and explains some of the side effects elicited by D2R blockers when used in neurological and psychiatric conditions, including schizophrenia, bipolar disorder, Tourette's syndrome, dementia, alcohol-induced delusions and obsessive-compulsive disorder.

Red wine intake but not other alcoholic beverages increases total antioxidant capacity and improves pro-inflammatory profile after an oral fat diet in healthy volunteers.

INTRODUCTION: Different alcoholic beverages exert different effects on inflammation and oxidative stress but these results are controversial and scanty in some aspects. We analyze the effect of different alcoholic beverages after a fat-enriched diet on lipid profile, inflammatory factors and oxidative stress in healthy people in a controlled environment. METHODS: We have performed a cross-over design in five different weeks. Sixteen healthy volunteers have received the same oral fat-enriched diet (1486kcal/m(2)) and a daily total amount of 16g/m(2) of alcohol, of different beverages (red wine, vodka, brandy or rum) and equivalent caloric intakes as sugar with water in the control group. We have measured the levels of serum lipids, high sensitivity C-reactive protein (hsCRP), tumor necrosis factor α (TNFα), interleukin 6 (IL-6), soluble phospholipase A2 (sPLA2), lipid peroxidation (LPO) and total antioxidant capacity (TAC). RESULTS: Red wine intake was associated with decreased of mean concentrations of hsCRP, TNFα and IL-6 induced by fat-enriched diet (p<0.05); nevertheless, sPLA2 concentrations were not significantly modified. After a fat-enriched diet added with red wine, TAC increased as compared to the same diet supplemented with rum, brandy, vodka or the control (water with sugar) (p<0.05). CONCLUSIONS: Moderate red wine intake, but not other alcoholic beverages, decreased pro-inflammatory factors and increased total antioxidant capacity despite a fat-enriched diet intake in healthy young volunteers.

A biodistribution study of PEGylated PCL-based nanoparticles in C57BL/6 mice bearing B16/F10 melanoma.

One of the major drawbacks that limits the clinical application of nanoparticles is the lack of preliminary investigations related to their biocompatibility, biodegradability and biodistribution. In this work, biodegradable PEGylated polymer nanoparticles (NPs) have been synthesized by using macromonomers based on poly(ε-caprolaconte) oligomers. More in detail, NPs have been produced by adopting a surfactant-free semibatch emulsion polymerization process using PEG chains as a stabilizing agent. The NPs were also labeled with rhodamine B covalently bound to the NPs to quantitatively study their biodistribution in vivo. NPs were investigated in both in vitro and in vivo preclinical systems to study their biodistribution in mice bearing B16/F10 melanoma, as well as their biocompatibility and biodegradability. The NP concentration was evaluated in different tissues at several times after intravenous injection. The disappearance of the NPs from the plasma was biphasic, with distribution and elimination half-lives of 30 min and 15 h, respectively. NPs were retained in tumors and in filter organs for a long time, were still detectable after 7 d and maintained a steady concentration in the tumor for 120 h. 48 h after injection, 70 ± 15% of the inoculated NPs were excreted in the feces. The favorable tumor uptake, fast excretion and absence of cytotoxicity foster the further development of produced NPs as drug delivery carriers.

Mode of action of trabectedin in myxoid liposarcomas.

To elucidate the mechanisms behind the high sensitivity of myxoid/round cell liposarcoma (MRCL) to trabectedin and the suggested selectivity for specific subtypes, we have developed and characterized three MRCL xenografts, namely ML017, ML015 and ML004 differing for the break point of the fusion gene FUS-CHOP, respectively of type I, II and III. FUS-CHOP binding to the promoters of some target genes such as Pentraxin 3 or Fibronectin 1, assessed by chromatin immunoprecipitation, was strongly reduced in the tumor 24 h after the first or the third weekly dose of trabectedin, indicating that the drug at therapeutic doses causes a detachment of the FUS-CHOP chimera from its target promoters as previously shown in vitro. Moreover, the higher sensitivity of MRCL types I and II appears to be related to a more prolonged block of the transactivating activity of the fusion protein. Doxorubicin did not affect the binding of FUS-CHOP to target promoters. Histologically, the response to trabectedin in ML017 and ML015 was associated with a marked depletion of non-lipogenic tumoral cells and vascular component, as well as lipidic maturation as confirmed by PPARγ2 expression in western Blot. By contrast, in ML004 no major changes either in the cellularity or in the amount of mature were found, and consistently PPARγ2 was null. In conclusion, the data support the view that the selective mechanism of action of trabectedin in MRCL is specific and related to its ability to cause a functional inactivation of the oncogenic chimera with consequent derepression of the adypocytic differentiation.

The blight of pollution keratoconjunctivitis among children in oil-producing industrial areas of Delta State, Nigeria.

The rapid urbanization and industrialization of Warri and environs between 1968 and 1990 have some adverse consequences due to accumulation of diverse categories of pollutants from drilling, production, and refining of crude oil and production of petrochemicals, especially black carbon. Persistent itching, foreign body sensation, and specified areas of conjunctival/limbal discoloration were used as markers for pollution keratoconjunctivitis (PKC). Children attending eye clinics in Delta State government hospitals located at Warri, Ekpan, and Aladja were sampled. Warri and Ekpan, both oil-producing areas, were used as the experimental group. Aladja, also within the same location but a nonoil-producing area (steel industries), was used as the control. The levels of black carbon and tetraethyl lead (TEL) were measured in the tear film of 100 children selected by a simple random technique from each location. Biochemical assays showed that the tear samples contained some levels of TEL among the sample population, and the TEL content was 0.01 microg/mL for all the tear samples. Stereomicroscopy gave the following estimated values of black carbon content washed off the external adnexia of the sample population: Ekpan 2%/mL, Warri 1.5%/mL, and Aladja 0.6%/mL. The results also show that occurrence of the three major clinical signs and symptoms of PKC (persistent itching, foreign body sensation, specified limbal/conjunctival discoloration, respectively) were as follow: Ekpan, 79, 68, and 65%; Warri, 55, 53, and 50%; Aladja, 26, 22, and 16%. This indicates that higher particulate concentrations of black carbon correlated with increased prevalence of the markers for manifestation of PKC. This implies that the markers for PKC in this experiment are more pronounced in oil-producing areas.

The under utilization of honey in a deprived environment.

The study investigated the utilization of honey in the treatment and prevention of illness amongst 400 respondents in Oranfe Community, Ile-Ife, Osun State Nigeria. Data were collected by employing a structured and pretested open ended questionnaire. The data indicated that 21%, 17% and less than 5% of the respondents had used honey for wounds, respiratory tract infections and gastroenteritis respectively. Neither educational nor professional status had any significant influence on the usage of honey in the treatment and prevention of common illness (p > 0.05). The vast majority (55%) preferred refined sugar to honey. The study has some policy implications. The first is the need for an intensive nutrition education programme that will disseminate the health benefits of honey as a source of energy, essential nutrients and its antioxidant properties. The second is the need to promote its usage in clinical trials because of its antibacterial properties.

Childhood-onset congenital adrenal hyperplasia: long-term outcome and optimization of therapy.

Congenital adrenal hyperplasia is a general term applied to several disorders caused by inherited recessive defects of cortisol synthesis. The most common form is 21-hydroxylase deficiency, accounting for 95% of cases. The classical forms have an incidence of one in 15,000 and the non-classical forms about one in 1,000. The classical or severe phenotype presents in the newborn period or early infancy with virilization and adrenal insufficiency, with or without salt-losing; the non-classical or mild phenotype presents in late childhood or early adulthood with signs of hyperandrogenism. This wide range of clinical expression is explained by genetic variation. Although there is a certain amount of genotype-phenotype correlation, discrepancies have been described. During the last 30 years there has been a substantial improvement in diagnosis and treatment of this disease, and patients with CAH now reach adulthood. Treatment of this condition is intended to reduce excessive corticotropin secretion and replace glucocorticoids and mineralocorticoids as physiologically as possible. Clinical management is often complicated by periods of inadequately treated hyperandrogenism, iatrogenic hypercortisolism, or both. Long-term consequences in adult life may include short stature, obesity, diminished bone mass, gonadal dysfunction with low fertility rates and psychosexual dysfunction in females. New treatment approaches are under investigation, such as the use of anti-androgens, inhibitors of estrogen production and adrenalectomy for severely resistant cases.

Impairment of renal vasodilation with l-arginine is related to more severe disease in untreated hypertensive patients.

Data remain insufficient to place the decreased response to L-arginine in hypertensive patients within a consistent pathophysiological sequence. The aim of the present study in patients with essential hypertension was to assess the relationships between the response to L-arginine and a set of relevant clinical and laboratory parameters. In this prospective, interventional study, we administered L-arginine to untreated hypertensive individuals and healthy control subjects and measured the clearance of inulin and of para-aminohippurate and a set of biochemical and clinical variables. L-Arginine infusion revealed major differences between control subjects and 1 subgroup (group B) of hypertensive individuals. Group B hypertensives (n=18) had no increase in inulin clearance and no decrease in renal vascular resistance with L-arginine; however, in another subset of hypertensive patients (group A, n=27), the insulin clearance increased and renal vascular resistance decreased similar to the control group (group C, n=11). The ambulatory blood pressure monitoring in group B showed both an increased mean diastolic pressure and a "nondipper" pattern in the nocturnal regulation of arterial pressure. These findings in group B were accompanied by significant alterations in optic fundus and left ventricle hypertrophy and increased microalbuminuria (all, P<0.05). Furthermore, group B individuals had significantly lower values of HDL cholesterol and a higher baseline atherogenic index, plasma insulin level, and glucose/insulin index. We disclose a previously undescribed relationship between end organ repercussion and decreased renal hemodynamic response to L-arginine. Our results may help to understand the mechanisms that lead to target organ damage in hypertension.

Lipoabdominoplasty without undermining.

BACKGROUND: The classic abdominoplasty still provides the best aesthetic results, despite many advances in abdominoplasty techniques. However, this procedure is associated with a relatively high incidence of complications. OBJECTIVE: A new technique is described that combines lipoplasty with traditional abdominoplasty without undermining of the abdominal flap. METHODS: Lipoplasty proceeds from the region above the umbilicus to the flanks and the region below the umbilicus. The skin below the umbilical scar is resected as in classical abdominoplasty, but a thinner fatty layer with its connective tissue, lymphatic vessels, and blood vessels is preserved. Complementary lipoplasty is performed if necessary to remove excess fat. RESULTS: The procedure results in an improved body shape, better accommodation of the abdominal flap, and a more youthful appearance of the abdomen with less scarring and no incidence of "dog ears" or major complications. CONCLUSIONS: Lipoabdominoplasty without undermining enhances aesthetic results with fewer complications than traditional abdominal aesthetic surgery. Aesthetic Surg J 2001;21:518-526.).

[Increase of tubular secretion of creatinine by L-arginine: mechanism of practical significance in the assessment of renal function based on creatinine clearance]. / Aumento de la secreción tubular de creatinina por L-arginina: un mecanismo con importancia práctica en la evaluación de la función renal por medio del aclaramiento de creatinina.

BACKGROUND: Tubular secretion of creatinine is increased by meat meals. This increment has been attributed to the formation of new creatinine from creatine contained in the cooked meals. However, no studies are available using amino acid infusions containing no creatine, which allow to further investigate the putative causes of increment in tubular creatinine secretion. METHODS: We performed a prospective, interventional study involving 34 individuals with normal renal function participating in a protocol on arterial hypertension. A continuous infusion of L-arginine (6%, i.v., in four 30 min periods at 50, 100, 200 and 300 ml/h) was administered. Creatinine (CCr) and inulin (CIn) clearances were determined at baseline and during L-arginine infusion. We analyzed the effects of L-arginine on tubular secretion by comparing CCr and CIn and calculated tubular secretion of creatinine (TSCr). RESULTS: L-arginine infusion induced a significant increase in both CCr and CIn. CCr and CIn were respectively 117.9 +/- 22.7 and 107.5 +/- 23, before and 170.3 +/- 23 and 144.2 +/- 47.8 after the infusion of L-arginine (both p < 0.01). This increase was simultaneous with an increment in TSCr from 1.12 +/- 0.4 to 1.43 +/- 0.6 (p < 0.01). CCr correlated significantly with CIn at baseline and at 60 min of infusion (r = 0.365, p = 0.031 and r = 0.368, p = 0.038, respectively), but not at 120 min (r = 0.130, p = 0.412), a time corresponding to the maximum increase in CIn and TSCr. CONCLUSIONS: L-arginine induces a substantial increase of CCr, which exceeds that expected from the increase in glomerular filtration rate measured by CIn and corresponds to an increment in TSCr. This phenomenon adds a new interpretation of the effect of amino acids on tubular handling of creatinine and has practical implications in the evaluation of renal function by means of creatinine clearance.

Increased expression of vascular endothelial growth factor in pyogenic granulomas.

The expression of vascular endothelial growth factor (VEGF) was analysed in biopsy samples from patients with pyogenic granuloma. The results disclosed the presence of a strong VEGF signal in pyogenic granulomas, which are constituted by a vast majority of cells of endothelial lineage. A marked positivity was evident in areas of proliferating endothelial cells without vessel lumen formation. In the same respect, staining for VEGF was less marked in the vessels with a well-developed lumen. The fact that VEGF production appears to be limited to endothelial cell precursors or immature endothelial cells prior to the complete development of the vessels, leads to the possibility that VEGF may act as an autocrine factor in circumstances of endothelial cell stimulation.

[In old age ... AIDS. Is it worth to initiate antiretroviral treatment? Review of 37 patients more than 60 years of age]. / A la vejez ... el SIDA. Merece la pena iniciar tratamiento antirretroviral? Revision de 37 pacientes con más de 60 años.

INTRODUCTION: HIV infection is common in young persons and its clinical picture, outcome and response to antiretroviral therapy is well known, but it is not the case in the elderly. OBJECTIVES: To evaluate the clinical characteristics and response to antiretroviral therapy of HIV elderly patients. DESIGN: Retrospective study of 37 patients elder than 60 years. The control group comprised of 64 HIV positive patients with less than 60 years. None of them were drug abusers. RESULTS: The mean age of patients was 65 years (range 60-79), 86% were males. The most frequent causes for HIV testing were: wasting (22%), P. carinii pneumonia (19%), tuberculosis (13%) and Kaposi sarcoma (10%), but in the control group voluntary testing was the most common reason (64%). The mean CD4 count at diagnosis was lower in the elderly group (233 cells/microL vs 323 cells/microL). During follow up, the most frequent complications for those with less than 200 CD4 cells were: oral candidiasis (44%), P. carinii pneumonia (27%), Kaposi sarcoma (22%) and esophageal candidiasis (22%), while in the young group P. carinii pneumonia (22%), Kaposi sarcoma (9%) and esophageal candidiasis (9%) were less frequent. 67% of the elderly received antiretroviral therapy. Zidovudine had to be discontinued due to anaemia in half of them. Survival at 6 and 12 months was significantly longer in treated patients compared to those who did not received antiretrovirals (100% vs 14% at 6 months, P < 0.001; and 54% vs 0% at 12 months, p = 0.03); and at 2 years it was almost similar to that of the young group (36% vs 52%, p = 0.38). CONCLUSIONS: HIV infection in the elderly is generally diagnosed in an advance stage, but antiretroviral therapy prolongs survival. Zidovudine should be reserve as a second line drug because its frequent haematological toxicity.

Hyperkalemia in patients infected with the human immunodeficiency virus: involvement of a systemic mechanism.

BACKGROUND: The appearance of hyperkalemia has been described in human immunodeficiency virus (HIV)-positive patients treated with drugs with amiloride-like properties. Recent in vitro data suggest that individuals infected with HIV have alterations in transcellular K+ transport. METHODS: With the objective of examining the presence of alterations in transmembrane K+ equilibrium in HIV-positive patients, we designed a prospective, interventional study involving 10 HIV-positive individuals and 10 healthy controls, all with normal renal function. An infusion of L-arginine (6%, intravenously, in four 30-min periods at 50, 100, 200, and 300 ml/hr) was administered, and plasma and urine electrolytes, creatinine, pH and osmolality, total and fractional sodium and potassium excretion, transtubular potassium gradient, plasma insulin, renin, aldosterone, and cortisol were measured. RESULTS: A primary disturbance consisting of a significant rise in plasma [K+] induced by L-arginine was detected in only the HIV patients but not in the controls (P < 0.001 between groups). A K+ redistribution origin of the hyperkalemia was supported by its rapid development (within 60 min) and the lack of significant differences between HIV-positive individuals and controls in the amount of K+ excreted in the urine. The fact that the HIV-positive individuals had an inhibited aldosterone response to the increase in plasma K+ suggested a putative mechanism for the deranged K+ response. CONCLUSIONS: These results reveal that HIV-infected individuals have a significant abnormality in systemic K+ equilibrium. This abnormality, which leads to the development of hyperkalemia after the L-arginine challenge, may be related, in part, to a failure in the aldosterone response to hyperkalemia. These results provide a new basis for understanding the pathogenesis of hyperkalemia in HIV individuals, and demonstrate that the risk of HIV-associated hyperkalemia exists even in the absence of amiloride-mimicking drugs or overt hyporeninemic hypoaldosteronism.

Induction of microalbuminuria by l-arginine infusion in healthy individuals: an insight into the mechanisms of proteinuria.

Despite evidence from individuals with diabetes mellitus or reduced renal mass, the actual relationship between protein- or amino acid-induced changes in renal function and urinary albumin excretion (UAE) is largely unknown in subjects without renal disease. In humans, infusions of l-arginine have been used recently in vascular and renal pathophysiological studies. The present study was undertaken to analyze the mechanisms involved in a particular effect; namely, the behavior of UAE during amino acid loading. A prospective interventional protocol was performed on 10 healthy adults by means of an intravenous infusion of l-arginine. The main results show that l-arginine induced a significant increase in UAE from 13.1 +/- 3.8 before to 53.3 +/- 11.1 microgram/min after the infusion (P < 0.005). This increment was simultaneous to an increase in glomerular filtration rate (GFR) and renal plasma flow (RPF). Furthermore, l-arginine markedly increased the urinary excretion of beta2-microglobulin. UAE correlated significantly with GFR (r = 0. 738; P = 0.014) and RPF (r = 0.942; P < 0.0001), but not with urinary beta2-microglobulin (r = 0.05; P = not significant). Furthermore, marked differences (P = 0.001) were found between the percentage of increase in UAE (306.8% +/- 163.2%) with respect to either albumin filtered load (FLAlb; 57.9% +/- 16.3%) and beta2-microglobulin excretion (1,088.5% +/- 424.6%). No changes were found in vehicle-infused individuals. In conclusion, the present study shows, in controlled conditions, that l-arginine infusion induces a relevant increase in UAE in healthy individuals that significantly exceeds that expected from the increase in GFR alone. The intense and simultaneous increment in beta2-microglobulin excretion strongly suggests that the effect of l-arginine on UAE is, in a relevant part, mediated through a blockade in the tubular protein reabsorption pathways. However, the profound differences observed in the changes induced by l-arginine on UAE and beta2-microglobulin excretion and the differences in the correlation of UAE and beta2-microglobulin with respect to GFR suggest that substantial diversity exists in the mechanisms by which l-arginine affects the renal management of albumin and beta2-microglobulin. These findings are relevant for understanding the renal response to l-arginine and protein/amino acid loads.

Cardiopulmonary bypass and circulatory arrest increase endothelin-1 production and receptor expression in the lung.

BACKGROUND: Endothelin-1 has been shown to be a mediator of pulmonary hypertension after cardiopulmonary bypass and deep hypothermic circulatory arrest. It is not known whether the mechanism is increased production of endothelin-1 or alterations in expression of endothelin-1 receptors in the lung. This study was designed to test the hypothesis that circulatory arrest increases endothelin-1 mRNA levels and endothelin-1 receptor expression in the lung. METHODS AND RESULTS: Twenty-four piglets (7 to 30 days old) were studied randomly either at baseline (controls, n = 12) or after cardiopulmonary bypass with 30 minutes of circulatory arrest (deep hypothermic circulatory arrest, n = 12). Lungs and pulmonary arteries were harvested immediately after hemodynamic data collection. Deep hypothermic circulatory arrest significantly increased pulmonary vascular resistance (p < 0.01). Deep hypothermic circulatory arrest also produced a significant increase in endothelin-1 mRNA levels in the pulmonary arteries (149 +/- 55 pg vs 547 +/- 111 pg, p = 0.007). There was no significant change in the pulmonary parenchymal endothelin-1 mRNA levels (4102 +/- 379 pg vs 4623 +/- 308 pg, p = 0.32). Ligand binding studies of the lung parenchyma revealed a single specific endothelin-1 binding site with an EC50 value (effective concentration causing 50% of the maximum response) of about 1 x 10(-8) mol/L, consistent with the endothelin B subtype. Deep hypothermic circulatory arrest resulted in a significant increase in the number of endothelin-1 receptors in the lung (109 +/- 6 fmol/mg total protein to 135 +/- 9 fmol/mg total protein, p = 0.02). CONCLUSIONS: Deep hypothermic circulatory arrest increases production of endothelin-1 by the pulmonary vascular endothelium. Endothelin-1 production in the pulmonary parenchyma does not change. Expression of endothelin B receptors in the pulmonary parenchyma also increases after cardiopulmonary bypass with deep hypothermic circulatory arrest. This study supports the hypothesis that deep hypothermic circulatory arrest results in pulmonary vascular endothelial activation with increased endothelin-1 mRNA production.