Urine therapy through the centuries.

Urine has always interested and attracted the attention of people. It was in fact never considered a waste product of the body but rather as a distilled product selected from the blood and containing useful substances for the care of the body. It was referred to as the "gold of the blood" and "elixir of long life," indicating its therapeutic potential. This paper reports on the practice of urine therapy since its origin attributed to the Indian culture, and briefly reviews its use through the centuries and different cultures and traditions. Records from the Egyptians to Jews, Greeks, Romans and from the Middle Ages and the Renaissance testify to the practice of urine therapy--a practice that continues to be found in more recent times, from the 18th century to the present. Experiences with the practice of urine therapy have even been discussed and shared recently in 2 different conferences: in 1996 in India and in 1999 in Germany, where people from different countries shared and presented their own research on urine therapy.

Abnormal distribution of sarcoglycan subcomplex in colonic smooth muscle cells of aganglionic bowel.

Hirschsprung's disease (HD) is a development disorder of the enteric nervous system in which the altered innervation explains the inability of the aganglionic segment to relax. Impairment of cytoskeleton in SMC of aganglionic bowel has been shown. Sarcoglycan subcomplex (SG) may support the development and maintenance of muscle cells. We examined the SG subunit expression in colonic aganglionic and ganglionic specimens obtained from patients with HD. Full-thickness bowel specimens were obtained from six patients with HD. Six normal colon specimens were used as controls. Immunofluorescent analysis and reverse transcriptase polymerase chain reaction evaluation were performed for alpha-, beta-, gamma-, delta- and epsilon-SG. In control colon, the indirect immunofluorescence showed a strong staining pattern of beta- gamma- delta- and epsilon-SG while a weak positivity of alpha-SG was recorded. In aganglionic bowel, immunofluorescence intensity values documented a significant lack of epsilon-SG while an enhanced alpha-SG, coupled to a loss of epsilon-SG, was recorded in ganglionic bowel in HD-affected patients. Our observations underscore the assumption that non-neuronal elements of the colon might play a key role in the pathogenesis of HD and loss of epsilon-SG might critically alter the cytoskeleton in the aganglionic bowel segment. Up-regulation of alpha-SG is probably an acquired phenomenon to reinforce the sarcolemma and to perform a forceful contraction in dilated ganglionic HD-affected colon, related to chronic pseudo-obstruction, contributing to the intestinal dysmotility that persists in 20% of patients after resection of the aganglionic bowel.

Phosphorus: the philosopher's stone discovered in 1669.

Recently the importance in nephrology of phosphorus as phosphate has been highlighted by chronic renal failure patients, in whom the toxic effect of phosphate is widely acknowledged, given the association of phosphate serum level with cardiovascular risk. This association is not limited to chronic renal failure and hemodialysis patients as high serum phosphate. Recently high serum phosphate levels were associated with increased risk for cardiovascular disease in subjects free from chronic kidney disease, and cardiovascular disease as well, and with progression of atherosclerosis. It is useful to know the history of phosphorus from its discovery in 1669, because that history gives us more evidence to better understand the negative and/or toxic effects of high phosphate serum levels and to identify phosphorus as a physiologically crucial anion.

Impotence in the 18th and 19th century: concepts of etiology and approaches to therapy.

The old word impotence is derived from the Latin word impotencia, which literally translated means "lack of power." Impotence, in the course of the history, has been attributed to mental pathology, anxiety, or demons or witches. Historically, the pharmacological treatments for impotence started in Greek times, when a myriad of herbal medications were applied locally to the genitals to enhance "sexual strength." In the 18th century, theories about the main factors inducing impotence saw it as an abnormal state of the fibers, a defect in the solid or liquid substances or a bad structure (tumor, inflammation, abscess, ulcer or foreign body). According to these mechanisms, when impotence depended on the state of the muscular fibers, treatment included a tepid bath and a clyster. In very fat or very weak people, who get particularly tired, it was important to use the remedies able to give energy to the fibers, such as ferrous mineral waters, for a month. Moreover, other suggestions were to ride a horse, to sleep few hours, to breathe good country air, to take a purge every 2 weeks, to drink half a glass of wine from Borgogne or to distract the mind continuously. In the 19th century, therapies regarding impotence included slight electric stimulation through the application of stimulators on the scrotum in the testis or epididymis areas, until pain was induced. In the same period, another method for treating impotence was flagellation. This method consisted of little flagellations with leather strips.

Salivary phosphorus and phosphate content of beverages: implications for the treatment of uremic hyperphosphatemia.

BACKGROUND: Hyperphosphatemia provides relevant and dangerous evidence of end-stage renal disease (ESRD) in patients undergoing periodic hemodialysis. The relationship between hyperphosphatemia and cardiovascular calcification, with the consequences of high morbidity and mortality after cardiovascular events, is well-defined. Hyperphosphatemia is treated by dietary limitation of phosphorus ingestion and by phosphate binders, but only half of ESRD patients fall within the range of K/DOQI guidelines. OBJECTIVE AND METHODS: We summarize the results of our studies on salivary phosphate secretion in hemodialysis (HD) and chronic kidney disease (CKD) patients, and on the habit of HD patients to drink beverages with a high or low phosphate content. We also examine the correlation between hyperphosphoremia and the phosphate content of common beverages consumed by HD patients. RESULTS AND CONCLUSIONS: Higher levels of salivary phosphate secretion were found in HD and in CKD patients, along with a relationship between serum phosphorus levels and a high phosphate content of beverages in HD patients.

Sexual dysfunction in chronic renal failure.

Recent studies have shown that testosterone is involved in the pathogenesis of cardiovascular diseases. Moreover, in observational studies blood testosterone concentrations, resulted consistently lower, not only among men with cardiovascular disease but also in men with uremia. In order to correlate the blood level of testosterone with the degree of erectile dysfunction (ED) and chronic renal failure (CRF) (stage I-V) we selected a group of patients with renal failure on conservative treatment, who attended our nephrology outpatients clinic. All the patients had stage II and III renal failure, respectively with a creatinine clearance between 59-30 and 29-15 ml/m'. The sexual evaluation was done using a 15-item questionnaire, i.e. the International Index of Erectile Function (IIEF). Mean score of patients with ED were significantly lower than mean scores for healthy controls for all 15 questions (all p values <0.01). Preliminary results show a direct correlation between -IIEF and glomerular filtration rate (GFR) (R2 0.08); an inverse correlation between testosterone and cholesterol (R2 0.045); a higher number of diabetic patients with lower levels of testosterone, at level 3 of CRF; low levels of testosterone for smokers especially in stage II (GFR). These data confirm the direct correlation between ED and renal failure, and the role of diabetes and smoking in hypotestosteronemia, in patients with different degrees of renal insufficiency. Further prospective studies are needed in order to correlate cardiovascular morbidity and mortality in patients with CRF and blood levels of testosterone.

Sevelamer carbonate in the treatment of hyperphosphatemia in patients with chronic kidney disease on hemodialysis.

Sevelamer carbonate is an anion exchange pharmaceutical, developed to improve on the performance of the non-absorbable, non-calcium, and metal-free phosphate binder sevelamer hydrochloride. Sevelamer carbonate is expected not to worsen metabolic acidosis, as previously reported during long-term treatment with sevelamer hydrochloride in hemodialysis (HD) patients. Carbonate is the alternate counterion to chloride on the sevelamer polymeric backbone, but the active poly(allylamine) responsible for phosphate (PO4) binding remains unaltered. Therefore, sevelamer carbonate is expected to reduce elevated serum phosphorus level, similarly to sevelamer hydrochloride. Sevelamers are prescribed in uremic HD patients to control hyperphosphatemia, but the carbonate has also been proposed for the treatment of chronic kidney disease (CKD) non-dialysis patients. Although hyperphosphatemia is regarded as a main contributor to increased mortality in the HD population because of cardiovascular calcification, metabolic acidosis has also been advocated as a major player in the increased mortality in this population, by engendering malnutrition, negative nitrogen balance, and inflammation. This paper reviews the evidence showing that sevelamer carbonate is as good as sevelamer hydrochloride in terms of hyperphosphatemia control in CKD, but with a better outcome in serum bicarbonate balance.

Phosphate salivary secretion in hemodialysis patients: implications for the treatment of hyperphosphatemia.

BACKGROUND/AIMS: Hyperphosphatemia is recognized as contributing to the increased risk of cardiac death in end-stage renal disease (ESRD) and hemodialysis (HD) patients. Currently available pharmacologic treatment for hyperphosphatemia is based on phosphate binders but, despite treatment, only half of the patients fall within the range for serum phosphorus of the K/DOQI guidelines. Therefore, there is a need to identify other therapeutic approaches in order to reduce serum phosphate. Salivary fluid contains phosphate which, if related to the daily salivary secretion (1,000-1,880 ml), may raise interest in order to identify further additive approaches to phosphorus removal in uremic patients, while data about salivary phosphate secretion in ESRD patients are controversial. METHODS: This study evaluates salivary phosphate secretion in 68 HD patients compared with 30 healthy subjects. Saxon's test confirmed normal salivary function in patients and controls. Salivary calcium and serum phosphate, calcium and PTH were also measured. RESULTS: HD patients had significantly higher salivary phosphorus levels compared with healthy controls: 30.35 (26.5-34.6) vs. 12.1 (10.58-14.73) mg/dl (p < 0.0001), and this significantly correlated (p < 0.0001) with serum phosphorus. Multiple regression analysis confirmed serum phosphorus as the only predictor (p < 0.0001) of salivary phosphorus. CONCLUSIONS: Given the functional secretive similarity between salivary glands and the kidneys, this increased salivary phosphate secretion might be interpreted as being compensatory in the presence of renal failure. Absorption of the increased salivary phosphate secretion, however, may worsen hyperphosphatemia; therefore, the binding of salivary phosphate might be considered as a further therapeutic approach to hyperphosphatemia in ESRD.

Impotence in the XVIII-XIX century as described by Gian Pietro Fusanacci and Tommaso Eduardo Beatty.

In 1992, the definition of erectile dysfunction (ED) replaced the old term of impotence that had been used for many centuries, in order to avoid the general confusion existing until today in this field. In the past, the origin of impotence had been attributed to different causes such as psychological diseases, or witches and demons. In 1764, Fusanacci described impotence that can occur in the male as well as in the female, as a defect in reproduc-tion. The main causes responsible for impotence were identified as inability to achieve erection, a very fluid seminal ejaculation, a defective organ, dryness of testicles, and lack of copulative power after many sexual intercourses with healthy women. Some decades later in 1847, Beatty affirmed that one of the most remarkable changes that can be observed in the passage from childhood to maturity is the development of the sexual organs, followed by the appearance of new sensations. He distinguished impotence that occurs only in men from sterility that for him affects women, and divided the causes of impotence into 3 classes: organic, functional and moral (today defined as psychological). For Beatty, the progress of knowledge had taken away magic and sorcery from the human mind and now it was widespread only among the lowest and most ignorant classes of humble people. In this way, he shows the evolution of medical science in XIX century in accepting only the rational explanation of the human diseases.

Nutritional status in hemodialysis patients: options for on-line convective treatment.

Although hemodialysis (HD) has improved the life expectancy of patients with end-stage renal disease (ESRD), uremic patients continue to experience high morbidity and mortality. Two of the most important risk factors for morbidity and mortality are protein-energy malnutrition (PEM) and inflammation. The causes for PEM in ESRD are numerous. The use of materials for dialysis, especially of the dialyzer membrane, is reported as one of the recognized causes for chronic inflammation in hemodialysis. We performed a 6-month prospective study examining the influence of on-line predilution hemodiafiltration on the inflammatory and nutritional status in a population of male hemodialysis patients using ultrapure dialysis fluid and polyamide dialyzers. We evaluated serum C-reactive protein, albumin, and transferrin and some nutritional parameters such as body mass index (BMI), phase angle (phi), fatty mass (FM), and free fatty mass (FFM) using bioelectrical impedance (BIA). Results showed significant amelioration of BMI and the re-equilibrium of the acute phase protein after on-line predilution hemodiafiltration. These results support the hypothesis that on-line predilution hemodiafiltration, as convective extracorporeal treatment, may be used to treat malnourished hemodialysis patients and to prevent malnutrition in the ESRD patient at risk for malnutrition.

L-arginine: a new opportunity in the management of clinical derangements in dialysis patients.

L-Arginine is an essential amino acid for infants and growing children, as well as for pregnant women. This amino acid is a substrate for at least 5 enzymes identified in mammals, including arginase, arginine-glycine transaminase, kyotorphine synthase, nitric oxide synthase, and arginine decarboxylase. L-arginine is essential for the synthesis of creatine, urea, polyamines, nitric oxide, and agmatine. Arginine may be considered an essential amino acid in sepsis, and its supplementation could be beneficial in this clinical setting by improving microcirculation and protein anabolism. Rats receiving arginine-supplemented parenteral nutrition showed an increased ability to synthesize acute phase proteins when challenged with sepsis. Finally, L-arginine exerts antihypertensive and antiproliferative effects on vascular smooth muscles. It has been shown to reduce systemic blood pressure in some forms of experimental hypertension. Endothelial dysfunction and reduced nitric oxide bioactivity are associated with increased incidence of cardiovascular diseases. A beneficial effect of acute and chronic L-arginine supplementation on endothelial derived nitric oxide production and endothelial function has been shown. In end-stage renal disease patients, the rate of de novo arginine synthesis seemed to be preserved. Our preliminary data on a group of dialysis patients showed that predialysis arginine levels were stable in a normal range during the dialysis session and that hypertensive patients had lower arginine-citrulline ratio than normotensive patients.

Newer aspects of carnitine metabolism in uremia.

New knowledge on the physiologic role of L-carnitine and on the rationale of its use in patients on maintenance hemodialysis is provided. In particular, carnitine normalizes plasma and muscle carnitine levels and modifies both enzymatic pattern of muscle and morphology of single fibers, improving exercise tolerance. In addition, carnitine reduces erythropoietin requirements, the number of hypotensive episodes, improves ejection fraction, and decreases hospitalization.

Nutritional therapy in chronic kidney disease.

In patients with chronic kidney disease (CKD), specialized nutritional therapy may help reduce the risk of electrolyte imbalances, vitamin deficiencies, and protein energy malnutrition. Protein-restricted diets may slow the progression of renal disease and decrease the risk of morbidity and mortality in patients with CKD. In this review, we discuss some of the major nutritional concerns in individuals with CKD and offer practical recommendations for dietary therapy.

Carnitine and hemodialysis.

Carnitine, gamma-trimethyl-beta-hydroxybutyrobetaine, is a small molecule widely present in all cells from prokaryotic to eukaryotic. It is an important element in the beta-oxidation of fatty acids. A lack of carnitine in hemodialysis patients is caused by insufficient carnitine synthesis and particularly by the loss through dialytic membranes, leading in some patients to carnitine depletion with a relative increase of esterified forms. The authors found a decrease in plasma-triglyceride and increase of high-density lipoprotein cholesterol (HDL-Chol) in dialysis patients during carnitine treatment. Many studies have shown that L-carnitine supplementation leads to improvements in several complications seen in uremic patients, including cardiac complications, impaired exercise and functional capacities, muscle symptoms, increased symptomatic intradialytic hypotension, and erythropoietin-resistant anemia, normalizing the reduced carnitine palmitoyl transferase activity in red cells. In addition, carnitine supplementation may improve protein metabolism and insulin resistance. Recently, carnitine supplementation has been approved by the US Food and Drug Administration not only for the treatment, but also for the prevention of carnitine depletion in dialysis patients. Regular carnitine supplementation in hemodialysis patients can improve their lipid metabolism, protein nutrition, antioxidant status, and anemia requiring large doses of erythropoietin, It also may reduce the incidence of intradialytic muscle cramps, hypotension, asthenia, muscle weakness, and cardiomyopathy.

Physical exercise increases urinary excretion of lipoxin A4 and related compounds.

Lipoxins (LX) are lipoxygenase-derived eicosanoids with potent anti-inflammatory activities and vascular bed-dependent vasodilatory actions. LX can be formed in vitro and in vivo in a number of conditions, and we have reported that immunoreactive LXA(4) (iLXA(4)) is physiologically excreted with human urine. Using a recently developed LX extraction method coupled to an ELISA, we examined whether iLXA(4) excretion was modified by strenuous exercise, which is known to trigger potential LX-forming events. Maximal exertion significantly increased iLXA(4) urinary excretion in nine healthy volunteers (0.061 +/- 0.023 vs. 0.113 +/- 0.057 ng/mg creatinine; P = 0.028). iLXA(4) levels returned to baseline after 6 h and increased, although at a smaller extent, after 24 h. A significant correlation (r = 0.988) was denoted between iLXA(4) ELISA measurements and reversed-phase high-performance liquid chromatography quantitation of a previously described urinary tetraene, confirming its LXA(4)-related nature. These findings show for the first time that an increase in excretion of LXA(4)-related compounds can be observed in response to strenuous exercise. This may be the reflection of an enhanced LX biosynthesis, which may represent a safeguard mechanism that keeps the inflammatory reaction triggered by physical stress under control.