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Biomedical subjects

M Marinelli

Publications and source records attributed to M Marinelli.

At least 91 records · Page 5Linked to original sources

Studies on renal function in healthy women with different degrees of induced potassium depletion. 2). Patterns of hypokalemic renal dysfunction.

In order to investigate the renal functional effects of potassium depletion (KD) we have submitted 20 healthy women to different potassium depletive treatments by dietary and pharmacological means. By changing these treatments we have obtained three KD groups with cumulative potassium deficit of 160 +/- 43 (KD1, n = 8), 198 +/- 22 (KD2, n = 6) and 214 +/- 54 mmol (KD3, n = 6). Another 20 subjects were also studied as controls in normal potassium balance (N group). In all subjects the renal function has been evaluated by clearance (cl.) technique both during induced hypotonic polyuria and subsequent moderate antidiuresis induced by low dose infusion of lysine-8-vasopressin (LVP). A renal dysfunction occurred in differences between these two groups, they have been pooled in a single KD2 + KD3 group. In this group as compared to N the following renal dysfunctions were observed during hypotonic polyuria: a) reduction in creatinine cl. (in absence of significant differences in mean arterial pressure); b) inhibition of the fractional reabsorption of chloride by diluting segments; c) depression of the diuretic response to water load. Moreover in KD the LVP was less effective in reducing the creatinine cl. while it became effective in reducing the fractional excretions of NaCl. These findings indicate that the degree of KD reached in the KD2 + KD3 group was adequate to induce a renal dysfunction similar to that occurring in conditions of chronic hypokalemia. It is probable that hypokalemia by itself along with changes of both prostaglandin and angiotensin renal systems are involved in this renal dysfunction.

Blood Pressure↗

Studies on renal function in healthy women with different degrees of induced potassium depletion. 3) Effective roles of prostanoids and angiotensin II in hypokalemic renal dysfunction.

By using two similar dietary and pharmacological patterns of potassium depletive treatment, two experimental groups--KD2 (n = 6) and KD3 (n = 6)--with cumulative potassium deficit not significantly different, were obtained. The basal values of plasma potassium concentration and PRA, as well as the expression of renal hypokalemic dysfunction were not significantly different. Paired studies in the absence and presence of indomethacin (KD2 group) or enalapril (KD3 group) were performed. The aim of the research was evaluation of the effective roles of prostanoid and angiotensin (AT) II systems in renal hypokalemic dysfunction. The results show that: 1) AT II and cortical vasodilating prostanoids exerted opposite effects on the preglomerular arteriolar tone; 2) medullary prostanoids antagonized the vasopressin effects. Therefore, in potassium depletion the decreased synthesis of cortical and medullary prostanoids, in the face of the increased generation of AT II, contributed to reducing the glomerular filtration rate and facilitate the expression of vasopressin action. These components of the renal hypokalemic dysfunction probably exert a protective role with regard to the urinary chloride and potassium losses.

Angiotensin II↗

Urinary prostanoid excretion in healthy women with different degrees of induced potassium depletion.

Plasma renin activity (PRA), urinary excretions of PGE2, 6-keto-PGF1 alpha (6KPGF), TXB2 and renal function were determined in healthy women both in normal potassium balance (N, n = 14) and in experimental potassium depletion (KD). KD was induced by natriuretic treatment--associated to replacement of net NaCl and water losses--in the presence of either normal (congruent to 50 mmol/d) or low (less than or equal to 10 mmol/d) dietary potassium intake. By using different depletive patterns, three groups with estimated cumulative potassium deficit (mean +/- SEM) of 124 +/- 38 (KD0, n = 8), 160 +/- 43 (KD1, n = 8) and 198 +/- 22 mmol (KD2, n = 6), respectively, were obtained. Renal function by the clearance (cl.) method and urinary prostanoid concentrations by the RIA method were estimated during hypotonic polyuria (oral water load) and subsequent moderate antidiuresis induced by a low-dose infusion of lysine-8-vasopressin. 1. In KD0 group the potassium depletive treatment was inefficacious in significantly reducing either the plasma potassium concentration (PK) or the urinary potassium excretion (UKV). The reductions of PK and UKV as well as the enhancement of PRA became significant in KD1 and KD2 groups. 2. The urinary prostanoid excretions were not significantly changed in the KD0 and KD1 groups while in the KD2 group they were reduced, mainly concerning the urinary 6KPGF excretion. 3. Furthermore in the KD2 group, with larger potassium depletion, some of the typical hypokalemic renal dysfunctions appeared. The data suggest that a pathophysiologically critical degree of potassium depletion is associated with an inhibited renal prostanoid synthesis as well as an increased renin secretion.

6-Ketoprostaglandin F1 alpha↗

Effects of experimental potassium depletion on renal function and urinary prostanoid excretion in normal women during moderate anti-diuresis.

The hypothesis that potassium depletion (KD) might play a role in stimulating the renal synthesis of prostanoids, and that these materials can contribute to hypokalaemic renal dysfunction, has been tested. Healthy women were studied either in normal potassium balance (N,n = 14), or in experimental KD. KD was induced by low dietary potassium intake (less than or equal to 10 mmol day-1) and natriuretic treatment, associated with replacement of net NaCl and water loss. By using different depletive patterns, two groups with estimated cumulative potassium deficits of 160 +/- 43 mmol (KD1, n = 8) and 198 +/- 22 mmol (KD2, n = 6), respectively, were obtained. Renal function by the clearance (cl.) method and urinary PGE2, 6-keto-PGF1 alpha, TxB2 concentrations by the RIA method were measured during hypotonic polyuria (oral water load) and subsequent moderate antidiuresis induced by the infusion of low-dose lysine-8-vasopressin (LVP). Compared to the N group, only in the KD2 group do glomerular and tubular dysfunctions typical of hypokalaemia and reduced prostanoid excretions (significant for 6-keto-PGF1 alpha and TxB2 but not for PGE2) appear during polyuria besides the significant reductions of plasma potassium concentration, urinary potassium excretion and the significant increase in plasma renin activity. During LVP infusion the urinary prostanoid excretions were all significantly lower in absence of significant differences in urinary flow rate. Concerning its renal effects, LVP lost its ability to reduce the creatinine cl., while expressing a trend towards reduction in fractional chloride excretion. Indomethacin pretreatment restored the LVP effect on creatinine cl. and increased the antichloruretic LVP effect (although not significantly). To the extent that urinary prostanoid excretions reflect their intrarenal synthesis, our data demonstrate that KD inhibits this biosynthesis. A depressed production of prostanoids endowed with vasodilating and chloruretic activity probably played a role in attenuating the renal vascular hyporeactivity and the urinary chloride dispersion induced by KD.

Adult↗

Evaluation by cardiopulmonary exercise test of DDDR versus DDD pacing.

UNLABELLED: In eight patients (age 62 +/- 6 years) a DDDR pacemaker was implanted for sick sinus syndrome (three cases) or second- and third-degree AV block (five cases). In five subjects chronotropic incompetence (maximal heart rate on effort < 110 beats/min) was present before implantation. One month after implantation the patients were randomized to DDDR or DDD pacing for 3 weeks each, with subsequent crossover, and at the end of each period a symptom limited cardiopulmonary exercise test (25 watts/2 min) was performed and the patients were requested to fill a symptoms questionnaire. RESULTS: DDDR pacing, compared to DDD, was associated with higher maximal heart rates (127 +/- 20 vs 110 +/- 27 beats/min, P < 0.02), higher [VO2 max (25.4 +/- 6.1 vs 21.5 +/- 7.8 mL/kg/per min, P < 0.03) and higher VO2 at the anaerobic threshold (20.3 +/- 5.0 vs 15.8 +/- 4.9 mL/kg per min, P < 0.03), without significant differences in mean exercise time (526 +/- 193 vs 472 +/- 216 sec, NS). The increase in VO2 max obtained in DDDR versus DDD was significantly related to the increase in maximal heart rate (r = 0.72, P < 0.05) and the increase in VO2 at the anaerobic threshold obtained in DDDR versus DDD was related to the increase in heart rate at the anaerobic threshold (r = 0.81, P < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Anaerobic Threshold↗

Standardization with synthetic 22-kDa monomer human growth hormone reduces discrepancies between two monoclonal immunoradiometric assay kits.

Discrepancies among different methods for assaying human growth hormone have been described in various studies. The two major sources of discordant results are the heterogeneity of the antibodies and the different standardization bases used by the assay manufacturers. We propose standardizing assays with 22-kDa biosynthetic monomer human growth hormone diluted with the diluents supplied by the kit manufacturers. In a study of two monoclonal immunoradiometric assays (Hybritech, specific for the 22-kDa monomer; Sorin, recognizing also a 20-kDa variant hormone), standardization with 22-kDa monomer human growth hormone reduced by 63% the differences in results for 44 serum samples from children. The use of 22-kDa human growth hormone as a common standard, highly pure and easily available in large quantities, could help limit the interpretative problems in growth diagnostics.

Antibodies, Monoclonal↗

Adenine arabinoside monophosphate and acyclovir monophosphate coupled to lactosaminated albumin reduce woodchuck hepatitis virus viremia at doses lower than do the unconjugated drugs.

The woodchuck was selected to study the efficacy of liver-targeted antiviral drugs on hepadnavirus replication. Nineteen woodchucks chronically infected with woodchuck hepatitis virus were treated with adenine arabinoside monophosphate or acyclovir monophosphate, either free or conjugated with the liver-targeting molecule lactosaminated human serum albumin. Circulating woodchuck hepatitis virus DNA levels remained unchanged in untreated animals and in those receiving the carrier lactosaminated human serum albumin alone; in contrast, they were consistently lower after 5 days of treatment with the antiviral drugs. Free and conjugated adenine arabinoside monophosphate were active at doses of 10 and 0.75 mg/kg, respectively, and free and coupled ACVMP were active at doses of 20 and 2.6 mg/kg, respectively. These results indicate that the dosages of adenine arabinoside monophosphate and acyclovir monophosphate required to inhibit hepadnavirus growth can be sharply reduced by coupling the drugs to lactosaminated human serum albumin.

Acyclovir↗

[Acinar-cell tumors of the minor salivary glands].

The authors present a rare case of acinic-cell tumor of minor salivary glands. In the dissertation are analyzed the clinical, histopathological and therapeutic aspects of this rare pathology.

Chronic Disease↗

Isotopic and nonisotopic assays for measuring somatotropin compared: re-evaluation of cutoff value in provocative tests.

Measurement of human growth hormone (hGH; somatotropin) concentrations in serum after provocative tests is crucial for diagnosing deficiencies in production of this hormone. Serum hGH can be measured by various immunoassays, isotopic and nonisotopic, with monoclonal or polyclonal antibodies: a cutoff value of 10 micrograms/L after provocative testing is usually used to distinguish normal from hGH-deficient children. Previous studies demonstrated discrepancies in hGH measurement by different radioisotopic immunoassays. Here we evaluated the responses of six different commercial assays, radioisotopic and nonisotopic, with monoclonal or polyclonal antibodies in a series of 16 provocative tests (stimulation with clonidine) in short children. A wide range of discrepant values was obtained with the different kits. A cutoff of 10 micrograms/L produced discordance of diagnosis among assays for two children, whereas complete agreement was reached for a cutoff value of 7 micrograms/L. Parallelism tests performed with hGH international standard, pure recombinant hGH, and a serum with high hGH content suggest that heterogeneity of the antibodies used by the manufacturers, even among monoclonal antibodies, is the main source of discordant results. Cutoff values and reference values must be established separately for each method proposed for routine use.

Adolescent↗