Angiotensin II and prostaglandin interactions on systemic and renal effects of L-NAME in humans.

For investigation of whether interactions between prostaglandins and angiotensin II modulate renal response to acute nitric oxide synthesis inhibition in humans, seven young volunteers who were kept on a 240-mM Na diet underwent four experiments with 90 min of infusion of 3.0 microg/kg.min(-1) NG-nitro-L-arginine methyl ester (L-NAME), each preceded by a 3-d treatment with placebo (PL), 50 mg of losartan (LOS), 75 to 125 mg of indomethacin (IND), or both drugs. Mean arterial pressure (MAP), GFR, effective renal plasma flow (ERPF), and Na excretion rate (UNaV) were measured at baseline and from 0 to 45 min and 45 to 90 min of L-NAME infusion. After PL, L-NAME reduced GFR by 5% at 45 min (P < 0.05) and by 9% at 90 min (P < 0.001), ERPF by 11 to 17% (P < 0.001), and UNaV by 28 to 45% (P < 0.001). MAP, unchanged at 45 min, rose by 5% (P < 0.001) at 90 min. LOS prevented pressor but not renal effects of L-NAME. With L-NAME+IND, MAP rose even at 45 min (+5%; P < 0.001 versus baseline) with a 10% rise at 90 min (P < 0.001). Changes in GFR (-13 to -20%), ERPF (-19 to -26%), and UNaV (-51 to -70%) were greater than those with L-NAME+PL or L-NAME+LOS (P < 0.05 to 0.001). With L-NAME+IND+LOS, MAP did not increase, and GFR, ERPF, and UNaV fell much less than with L-NAME+IND alone (P < 0.02 to 0.001) with no differences versus PL or LOS alone. Angiotensin II blockade does not affect renal changes caused by L-NAME but prevents their potentiation by prostaglandin inhibition. Thus, endogenous prostaglandins counteract renal actions of endogenous angiotensin II in Na-repleted humans even when nitric oxide synthesis is inhibited.     

Essential arterial hypertension and stone disease.

BACKGROUND: Cross-sectional studies have shown that nephrolithiasis is more frequently found in hypertensive patients than in normotensive subjects, but the pathogenic link between hypertension and stone disease is still not clear. METHODS: Between 1984 and 1991, we studied the baseline stone risk profile, including supersaturation of lithogenic salts, in 132 patients with stable essential hypertension (diastolic blood pressure of more than 95 mm Hg) without stone disease and 135 normotensive subjects (diastolic blood pressure less than 85 mm Hg) without stone disease who were matched for age and sex (controls). Subsequently, both controls and hypertensives were followed up for at least five years to check on the eventual formation of kidney stones. RESULTS: Baseline urine levels in hypertensive males were different from that of normotensive males with regards to calcium (263 vs. 199 mg/day), magnesium (100 vs. 85 mg/day), uric acid (707 vs. 586 mg/day), and oxalate (34.8 vs. 26.5 mg/day). Moreover, the urine of hypertensive males was more supersaturated for calcium oxalate (8.9 vs. 6.1) and calcium phosphate (1.39 vs. 0.74). Baseline urine levels in hypertensive females were different from that of normotensive females with regards to calcium (212 vs. 154 mg/day), phosphorus (696 vs. 614 mg/day), and oxalate (26.2 vs. 21.7 mg/day), and the urine of hypertensive females was more supersaturated for calcium oxalate (7.1 vs. 4.8). These urinary alterations were only partially dependent on the greater body mass index in hypertensive patients. During the follow-up, 19 out of 132 hypertensive patients and 4 out of 135 normotensive patients had stone episodes (14.3 vs. 2.9%, chi-square 11.07, P = 0.001; odds ratio 5.5, 95% CI, 1.82 to 16.66). Of the 19 stone-former hypertensive patients, 12 formed calcium calculi, 5 formed uric acid calculi, and 2 formed nondetermined calculi. Of the urinary factors for lithogenous risk, those with the greatest predictive value were supersaturation of calcium oxalate for calcium calculi and uric acid supersaturation for uric acid calculi. CONCLUSIONS: A significant percentage of hypertensive subjects has a greater risk of renal stone formation, especially when hypertension is associated with excessive body weight. Higher oxaluria and calciuria as well as supersaturation of calcium oxalate and uric acid appear to be the most important factors. Excessive weight and consumption of salt and animal proteins may also play an important role.     

Loaded hydroxylapatite-coated implants and uncoated titanium-threaded implants in distracted dog alveolar ridges

AIMS: The aim of this study was to determine the response of alveolar bone after it was augmented vertically with distraction osteogenesis, implanted with hydroxylapatite (HA)-coated implants and noncoated titanium-threaded implants, and subsequently loaded for 1 year. METHODS: Eight dogs each had 4 implants placed horizontally into an edentulous mandibular quadrant. After integration, a distraction osteogenesis device was fabricated in the laboratory. An osteotomy was made to allow the crest of the alveolar ridge to be distracted vertically. After 10 mm of vertical distraction, the distraction devices were stabilized with light cured resin. After bone fill of the distraction gap was radiographically confirmed in all dogs at 10 weeks, 2 implants were placed into the ridges. Four dogs had threaded titanium implants placed, and 4 dogs had threaded HA-coated implants placed, with 1 implant in the distracted bone and 1 implant in adjacent nondistracted bone, for both groups. After 4 months for implant integration, bridges were fabricated and secured to the implants with screws. Crestal bone levels were evaluated by radiographs through 1 year of function. Animals were killed after 1 year of loading for histologic evaluation. RESULTS: The vertical ridge augmentation averaged 8.8 +/- 1.0 mm after 10 weeks of healing after distraction. Analysis of variance indicated a significantly greater change from baseline for HA-coated implants and for distracted bone sites. Histologic examination showed that bone had formed between the distracted segments creating an augmented ridge. The average thickness of the labial cortex in the distraction gap was significantly thinner than the lingual cortex in distracted bone or the lingual and labial nondistracted cortical bone. The presence of a dental implant did not significantly affect cortical bone thickness. Serial sections showed that implants remained integrated and functional without soft tissue inflammation. CONCLUSION: Dental implants placed into alveolar ridges augmented with the technique of distraction osteogenesis were functional for the length of this study.     

Increased urinary 6-keto-PGF1 alpha excretion during water immersion is blunted by metoclopramide in normal man

Urinary excretion of 6-keto-PGF1 alpha and 2,3 dinor-6-keto-PGF1 alpha, as indices of the renal and systemic production of prostaglandins, was measured during water immersion in a group of 6 healthy volunteers both in the presence and absence of dopamine blockade by the dopamine receptor antagonist, metoclopramide. Urinary flow rate and excretion of both sodium and 6-keto-PGF1 alpha increased during water immersion, while plasma renin activity and plasma aldosterone were reduced. Urinary kallikrein and 2,3 dinor-6-keto-PGF1 alpha also tended to increase during water immersion. Administration of metoclopramide significantly reduced 6-keto-PGF1 alpha and sodium excretion during water immersion, but produced no changes in plasma renin activity or in 2,3 dinor-6-keto-PGF1 alpha. Plasma aldosterone concentrations after metoclopramide were similar to those observed in the pre-immersion period. An increased synthesis of the vasodilator and natriuretic prostacyclin in the kidney might play a role in the response to water immersion. The reduced sodium and 6-keto-PGF1 alpha excretion observed after metoclopramide administration suggests that dopamine might induce prostacyclin synthesis in the kidney during water immersion.     

Ouabain-resistant, frusemide-sensitive sodium efflux in human lymphocytes: a comparison of normotensive and hypertensive subjects

Peripheral blood lymphocytes were isolated at room temperature in a low sodium medium in 17 normotensive control subjects (NC) and 13 patients with essential hypertension (EHP). Lymphocyte sodium content was not significantly different between NC and EHP (3.1 +/- 0.5, n = 11, and 3.6 +/- 0.5, n = 10, respectively; means +/- SEM). The effect of frusemide on the ouabain-resistant rate constant of sodium efflux (KNao) from these lymphocytes into a sodium-free medium was measured. The frusemide-sensitive efflux rate constant was 75 +/- mus (n = 17) in controls and significantly lower in EHP (32 +/- 7 mus, n = 13, P less than 0.001). In human lymphocytes there is a ouabain-resistant, frusemide-sensitive fraction of sodium efflux into a sodium-free medium; this fraction may be reasonably attributed to a sodium-potassium cotransport system. This sodium transport pathway seems to be reduced in lymphocytes from EHP.     

Derivatives of the new ring system indolo[1,2-c]benzo[1,2,3]triazine with potent antitumor and antimicrobial activity.

Derivatives of the new ring system indolo[1,2-c]benzo[1,2,3]triazine 5 were synthesized by diazotization of substituted 2-(2-aminophenyl)indoles followed by an intramolecular coupling reaction of the diazonium group with the indole nitrogen. To obtain the indolobenzotriazine system it was necessary to protect the 3 position of the indole nucleus to avoid cyclization into the indolo[3,2-c]cinnoline system 4. Indolobenzotriazines 5a-g were evaluated in vitro for antitumor activity against a panel of leukemia-, lymphoma-, carcinoma-, and neuroblastoma-derived cell lines. Some compounds inhibited the proliferation of T and B cell lines at submicromolar concentrations, whereas their activity against solid tumor cell lines was in the micromolar range. When evaluated for their antifungal potential 5a,d inhibited some of the fungi tested, although at concentrations very close to those inhibiting the proliferation of human cells. On the contrary, all indolobenzotriazines proved fairly potent and selective inhibitors of Streptococcus and Staphylococcus. In particular 5b,c,g were up to 80 times more potent than the reference drug streptomycin and inhibited the growth of the above Gram-positive bacteria at concentrations far lower than those cytotoxic for animal cells.     

Circulating opioid peptides during water immersion in normal man

1. This study was designed to evaluate variations in plasma beta-endorphin, methionine-enkephalin, adrenocorticotropic hormone and serum prolactin in healthy volunteers during head-out water immersion. 2. Water immersion induced an increase in methionine-enkephalin plasma levels, which was associated with a significant fall in mean arterial pressure and heart rate. 3. Conversely, a suppression of plasma beta-endorphin, adrenocorticotropic hormone and serum prolactin was detected during water immersion. 4. We suggest that a dopaminergic inhibitory control mechanism may be involved in regulating circulating levels of beta-endorphin, adrenocorticotropic hormone and prolactin in normal subjects undergoing extracellular fluid volume expansion produced by water immersion.     

Renin-angiotensin system unresponsiveness in phaeochromocytoma.

Water immersion to the neck is able to provoke a profound suppression of the renin-angiotensin system in several clinical conditions associated with hyper-reninaemia. Both hyper-reninaemia and secondary aldosteronism have sometimes been described in phaeochromocytoma. We report on two patients, with surgically proven phaeochromocytoma, in whom water immersion, performed before surgery, failed to induce any significant change in plasma renin activity.     

Analysis of the problem of "difficult hospital discharges" in the University Hospital of Parma

We analyzed, in a middle-sized hospital, the problems related to the so-called "difficult discharges", conceived as situations involving an economic, human and organizational burden exceeding patients' and their families' capacities and requiring a specific involvement of territorial services. During a whole year (July 1, 2001-June 30, 2002) the cases found were 591. We demonstrated that the problem concerns mainly elderly patients, almost equally distributed between males and females, a quarter of the sample being represented by patients who had recently undergone surgery and whose discharge difficulties were mostly related to mixed social and sanitary problems. This kind of patients is faced with long-term hospitalization implicating a large number of intra-hospital transfers due to the presence of severe and disabling pathologies, mainly neoplasms and strokes, often associated with other serious diseases, various complications and difficult situations from the health point of view. About half of the patients had the possibility to go back home, while the rest required lodging in territorial structures such as nursing homes and retirement homes. The average time-lapse between the possible discharge indicated by the hospital physician and the actual discharge was 10 days, with global annual 6106 days of "improper" hospitalization. Our conclusion is that the phenomenon of difficult discharges is nowadays a very topical problem and that it should be faced with a new model of continuous and integrated assistance organization.