Organ protection by SGLT2 inhibitors: role of metabolic energy and water conservation.

Therapeutic inhibition of the sodium-glucose co-transporter 2 (SGLT2) leads to substantial loss of energy (in the form of glucose) and additional solutes (in the form of Na+ and its accompanying anions) in urine. However, despite the continuously elevated solute excretion, long-term osmotic diuresis does not occur in humans with SGLT2 inhibition. Rather, patients on SGLT2 inhibitor therapy adjust to the reduction in energy availability and conserve water. The metabolic adaptations that are induced by SGLT2 inhibition are similar to those observed in aestivation - an evolutionarily conserved survival strategy that enables physiological adaptation to energy and water shortage. Aestivators exploit amino acids from muscle to produce glucose and fatty acid fuels. This endogenous energy supply chain is coupled with nitrogen transfer for organic osmolyte production, which allows parallel water conservation. Moreover, this process is often accompanied by a reduction in metabolic rate. By comparing aestivation metabolism with the fuel switches that occur during therapeutic SGLT2 inhibition, we suggest that SGLT2 inhibitors induce aestivation-like metabolic patterns, which may contribute to the improvements in cardiac and renal function observed with this class of therapeutics.

The ethanol metabolite acetaldehyde induces water and salt intake via two distinct pathways in the central nervous system of rats.

The sensation of thirst experienced after heavy alcohol drinking is widely regarded as a consequence of ethanol (EtOH)-induced diuresis, but EtOH in high doses actually induces anti-diuresis. The present study was designed to investigate the introduction mechanism of water and salt intake after heavy alcohol drinking, focusing on action of acetaldehyde, a metabolite of EtOH and a toxic substance, using rats. The aldehyde dehydrogenase (ALDH) inhibitor cyanamide was used to mimic the effect of prolonged acetaldehyde exposure because acetaldehyde is quickly degraded by ALDH. Systemic administration of a high-dose of EtOH at 2.5 g/kg induced water and salt intake with anti-diuresis. Cyanamide enhanced the fluid intake following EtOH and acetaldehyde administration. Systemic administration of acetaldehyde with cyanamide suppressed blood pressure and increased plasma renin activity. Blockade of central angiotensin receptor AT1R suppressed the acetaldehyde-induced fluid intake and c-Fos expression in the circumventricular organs (CVOs), which form part of dipsogenic mechanism in the brain. In addition, central administration of acetaldehyde together with cyanamide selectively induced water but not salt intake without changes in blood pressure. In electrophysiological recordings from slice preparations, acetaldehyde specifically excited angiotensin-sensitive neurons in the CVO. These results suggest that acetaldehyde evokes the thirst sensation following heavy alcohol drinking, by two distinct and previously unsuspected mechanisms, independent of diuresis. First acetaldehyde indirectly activates AT1R in the dipsogenic centers via the peripheral renin-angiotensin system following the depressor response and induces both water and salt intake. Secondly acetaldehyde directly activates neurons in the dipsogenic centers and induces only water intake.

Exogenous L-arginine attenuates the effects of angiotensin II on renal hemodynamics and the pressure natriuresis-diuresis relationship.

Administration of exogenous L-arginine (L-Arg) attenuates angiotensin-II (AngII)-mediated hypertension and kidney disease in rats. The present study assessed renal hemodynamics and pressure diuresis-natriuresis in anaesthetized rats infused with vehicle, AngII (20 ng/kg per min i.v.) or AngII + L-Arg (300 µg/kg per min i.v.). Experiments in isolated aortic rings were carried out to assess L-Arg effects on the vasculature. Increasing renal perfusion pressure (RPP) from ~100 to 140 mmHg resulted in a nine- to tenfold increase in urine flow and sodium excretion rate in control animals. In comparison, AngII infusion significantly reduced renal blood flow (RBF) and glomerular filtration rate (GFR) by 40-42%, and blunted the pressure-dependent increase in urine flow and sodium excretion rate by 54-58% at elevated RPP. Supplementation of L-Arg reversed the vasoconstrictor effects of AngII and restored pressure-dependent diuresis to levels not significantly different from control rats. Dose-dependent contraction to AngII (10(-10) mol/L to 10(-7) mol/L) was observed with a maximal force equal to 27 ± 3% of the response to 10(-5) mol/L phenylephrine. Contraction to 10(-7) mol/L AngII was blunted by 75 ± 3% with 10(-4) mol/L L-Arg. The influence of L-Arg to blunt AngII-mediated contraction was eliminated by endothelial denudation or incubation with nitric oxide synthase inhibitors. Furthermore, the addition of 10(-3) mol/L cationic or neutral amino acids, which compete with L-Arg for cellular uptake, blocked the effect of L-Arg. Anionic amino acids did not influence the effects of L-Arg on AngII-mediated contraction. These studies show that L-Arg blunts AngII-mediated vascular contraction by an endothelial- and nitric oxide synthase-dependent mechanism involving cellular uptake of L-Arg.

Involvement of bradykinin and prostaglandins in the diuretic effects of Achillea millefolium L. (Asteraceae).

ETHNOPHARMACOLOGICAL RELEVANCE: Achillea millefolium L. (Asteraceae), popularly known as "mil-folhas", is well recognized and widely used in Brazilian folk medicine to treat heart and kidney disorders. Among its popularly described effects are diuretic and hypotensive actions. AIM OF THE STUDY: The diuretic activity of Achillea millefolium L. extracts and its semi-purified fractions, as well as the mechanisms involved, were evaluated in male Wistar rats. MATERIAL AND METHODS: An aqueous extract (AEAM, 125-500 mg/kg), hydroethanolic extract (HEAM, 30-300 mg/kg), dichloromethane subfractions (DCM-2, 10 and 30 mg/kg), or hydrochlorothiazide (10mg/kg), were orally administered and the animals were kept in metabolic cages for 8h for urine collection. To evaluate the involvement of bradykinin and prostaglandins in the diuretic action of Achillea millefolium, selected groups of rats received HOE-140 (1.5mg/kg, i.p.) or indomethacin (5mg/kg, p.o.), before treatment with a DCM-2 subfraction (30 mg/kg). The urinary volume, conductivity, pH, density and electrolyte excretion were measured. RESULTS: Similar to hydrochlorothiazide, both HEAM and DCM-2, but not AEAM, increased urinary volume and the excretion of Na(+) and K(+) when compared with the control group (vehicle). The diuretic effect of DCM-2 was abolished by HOE-140 (a bradykinin B2 receptor antagonist), as well as by indomethacin (a cyclooxygenase inhibitor). CONCLUSION: The present study reveals that extracts obtained from Achillea millefolium are able to effectively increase diuresis when orally administered in rats. This effect depends on both the activation of bradykinin B2 receptors and the activity of cyclooxygenases.

Effects of high-tone external muscle stimulation on renal function in healthy volunteers.

OBJECTIVE AND DESIGN: Hightone external muscle stimulation (HTEMS) ameliorates pain and discomfort of patients with polyneuropathy. Since some patients reported about an urge to urinate during these treatments, the potential effects of HTEMS application on renal function were investigated. For this purpose in healthy subjects, we analyzed in the current study the acute effects of electrotherapy on parameters of renal function. INTERVENTIONS: 24 healthy volunteers (14 women and 10 men), mean age 26 ± 4 years, were enrolled. The protocol was composed of a run-in period, a pre-treatment period, the active HTEMS treatment period of both lower extremities and the post-treatment period. The duration of each period was 60 min. Urine collection and blood samples were taken at the beginning and end of each period. To achieve a sufficient diuresis, the fluid intake was adapted to the amount of diuresis. Parameters of renal function included diuresis, glomerular filtration rate (endogenous creatinine clearance) and absolute and fractional sodium excretion. Moreover blood pressure and heart rate were monitored. RESULTS: HTEMS led to a significant increase of creatinine clearance and fractional sodium excretion which was limited to the active treatment period. CONCLUSION: These findings show for the first time that HTEMS can transiently increase glomerular filtration rate associated with a decreased tubular sodium reabsorption. The underlying mechanisms are to be elucidated.

High-frequency external muscle stimulation in acute kidney injury (AKI): potential shortening of its clinical course.

BACKGROUND: The prognosis of acute kidney injury (AKI) is markedly influenced by the degree of muscle protein catabolism. Since the current therapeutic strategies are rather limited, for the first time, we attempted to attenuate the hypercatabolism by high tone electrical muscle stimulation (HTEMS) in AKI patients. This kind of therapy may lower protein degradation via its effect on muscle activity as well as improving insulin resistance. Moreover, electrotherapy may improve renal function due to circulatory effects as well as lowering the sympathetic tone. METHODS: 34 patients with AKI Stage 3 were included; all required daily hemodialysis with a dose of Kt/V urea > 1. The patients were randomized into two groups of 17 patients each with and without HTEMS. The groups were comparable with regard to age, gender, underlying diseases, causes of AKI and the baseline biochemistry. HTEMS was performed intradialytically for 1 h. This new electromedical device is characterized by changes in the frequency between 4,100 and 33,000 Hz in short intervals (3 s) and also the amplitude and frequency are modulated simultaneously. RESULTS: The treatment was well tolerated and associated with an improved clinical outcome. As compared to the untreated patients the HTEMS group showed a significant shorter duration of oliguria, a faster decline of serum creatinine and urea levels, less need of dialysis treatment and a shorter period of hospitalization. The decline of urea was more marked than that of serum creatinine resulting in a significant lowering of the urea/creatinine ratio. This finding suggests a reduced catabolism of muscle proteins which - via a lower release of amino acids into the circulation - results in a decline of hepatic ureapoiesis. We hypothesize that in our AKI patients the improved protein catabolism contributed to the shortening of the clinical course of acute renal failure. CONCLUSION: This study suggests for the first time that HTEMS treatment of patients with AKI during hemodialysis is associated with an improved clinical outcome. To support this novel observation, a randomized controlled trial with a greater number of homogenous AKI patients should be performed.

Intoxicación por sobredosificación de vitamina D en un lactante / Poisoning by overdose of vitamin d in an infant

El objetivo de esta nota técnica es la descripción y comentarios de un caso clínico reciente de intoxicación por sobredosificación por vitamina D, y la correcta interpretación clínica y de los parámetros de laboratorio. Caso clínico. Lactante de 6 meses en tratamiento con Biominol® (suplemento vitamínico), ingresó debido a un estado de decaimiento e irritabilidad. Las analíticas iniciales muestran concentraciones de calcio iónico en sangre de 2,11mmol/L (intervalo de referencia (IR): 1,15-1,29mmol/L), y concentración de calcio total plasmático de 5,5mmol/L (IR: 2,25-2,75mmol/L). En nuestro laboratorio, las vitaminas D2 y D3 fueron determinadas por cromatografía líquida de alta resolución (HPLC), y por un método electroquimioluminiscente, que mide la vitamina D total. Los valores de vitamina D2 fueron 419ng/mL y vitamina D total 482ng/mL (IR: 30-100ng/mL). La intoxicación de vitamina D tuvo origen exógeno, debido al incremento de vitamina D2. El diagnóstico definitivo fue hipercalcemia severa secundaria a intoxicación por vitamina D y nefrocalcinosis secundaria a esta con función renal normal con hipercalciuria. Como conclusión, cabe destacar la importancia de la correcta dosificación de los pacientes y la determinación de las diferentes formas de vitamina D para averiguar su origen, realizando una correcta interpretación (AU)

The objective of this technical note describes and comments on a recent clinical case of poisoning by overdose of vitamin D, and the correct interpretation of clinical and laboratory parameters. Vitamin D is a fat-soluble vitamin involved in the absorption of calcium and phosphorus in the intestine. Administration of high doses for prolonged periods can cause hypercalcemia, leading to kidney failure and renal calcifications. Clinical case. The definitive diagnosis of this patient was severe hypercalcemia secondary to exogenous vitamin D poisoning, and nephrocalcinosis secondary to this with normal renal function with hypercalciuria. In conclusion, the correct dosing of patients and determination of different forms of vitamin D to trace its origin and making a correct interpretation is important. Male, 6 months old in treatment with Biominol® (vitamin D supplement), was admitted to the emergency department because of a state of decline and irritability. The initial analytical results showed an ionized calcium concentration in blood of 2.11mmol/L (reference interval (RI): 1.15 - 1.29mmol/L), and plasma total calcium concentration of 5.5mmol/L (RI: 2.25-2.75mmol/L). In our laboratory, Vitamin D2 and D3 were determined by liquid chromatography high resolution (HPLC), and an electrochemiluminescence method. The results showed a vitamin D2 419ng/mL and total vitamin D 482ng/mL (RI: 30-100ng/mL). It was found that the vitamin D overdose was of exogenous origin, due to increased vitamin D2 (AU)

The antinociceptive activity of Polygonatum verticillatum rhizomes in pain models.

AIM OF THE STUDY: The current study was designed to establish the pharmacological rationale for the traditional use of the rhizomes of Polygonatum verticillatum in the treatment of painful conditions and as a plant diuretic. MATERIALS AND METHODS: The crude methanolic extract of the rhizomes of Polygonatumverticillatum (PR) was tested in various established pain models in rodents at 50, 100 and 200mg/kg i.p. while the diuretic activity was assessed at 300 and 600 mg/kg p.o. in rats. RESULTS: PR demonstrated significant reduction (14-72%) in the number of writhes induced by acetic acid in a dose-dependent manner. When nociceptive threshold was measured in the formalin test, PR strongly attenuated the formalin-induced flinching behaviour in both phases (6-30% in first phase while 12-72% in second phase). Central involvement in the analgesic profile of PR was confirmed by the hot plate test, in which PR elicited a significant (P<0.01) analgesic activity by increasing latency time. However, an opioid receptor antagonist, naloxone (2mg/kg s.c.) strongly antagonized the antinociceptive activity of PR. As a plant diuretic, PR showed mild but statistically insignificant diuretic activity at 300 mg/kg. The crude extract and solvent fractions of the plant contained reasonable quantity of total saponin and alkaloid contents. CONCLUSIONS: The mechanisms underlying the analgesic action of PR shows that the opioid dependant central mediation has synergistic effect by enforcing the peripheral analgesic effects. Interestingly, our findings not only substantiated the folk use of the plant as an analgesic but also reported for the first time in the whole genus.

The effect of desmopressin on renal water and solute handling in desmopressin resistant monosymptomatic nocturnal enuresis.

PURPOSE: We sought to evaluate the effect of desmopressin on renal water and solute handling in children with monosymptomatic nocturnal enuresis and desmopressin resistant nocturnal polyuria compared to healthy controls. MATERIALS AND METHODS: A total of 12 patients with enuresis and nocturnal polyuria, normal bladder reservoir function and no response to desmopressin, and 10 age matched controls were enrolled in the study. Children were admitted to the hospital for a 48-hour protocol comprising urine collections and blood sampling. Sodium and water intake was standardized. During the second night children received 40 mug intranasal desmopressin. Parameters characterizing the renal water and solute handling were measured and compared between baseline nights and nights with desmopressin. RESULTS: Desmopressin markedly reduced nocturnal urine output in patients with enuresis, minimizing sodium, urea and overall solute excretion, despite the fact that these children were unresponsive to desmopressin at home. This effect on renal sodium handling was not mediated by atrial natriuretic peptide, angiotensin II, aldosterone or renin. Desmopressin did not influence urinary prostaglandin E(2) excretion. The antinatriuretic effect was seen only in patients with enuresis, and it was directly correlated with the reduction in urine output. CONCLUSIONS: Children with nocturnal enuresis and nocturnal polyuria who do not exhibit adequate response to desmopressin at home seem to respond well to the agent at the clinic. The effect of desmopressin in children with enuresis seems largely dependent on reductions in the amount of sodium excreted. Sodium regulating hormones remained unaffected by desmopressin, indicating a possible direct effect of the agent on renal sodium handling.

Role of nitric oxide deficiency in the development of hypertension in hydronephrotic animals.

Hydronephrotic animals develop renal injury and hypertension, which is associated with an abnormal tubuloglomerular feedback (TGF). The TGF sensitivity is coupled to nitric oxide (NO) in the macula densa. The involvement of reduced NO availability in the development of hypertension in hydronephrosis was investigated. Hydronephrosis was induced by ureteral obstruction in young rats. Blood pressure and renal excretion were measured in adulthood, under different sodium conditions, and before and after chronic administration of either N(G)-nitro-l-arginine methyl ester (l-NAME) or l-arginine. Blood samples for ADMA, SDMA, and l-arginine analysis were taken and the renal tissue was used for histology and determination of NO synthase (NOS) proteins. TGF characteristics were determined by stop-flow pressure technique before and after administration of 7-nitroindazole (7-NI) or l-arginine. Hydronephrotic animals developed salt-sensitive hypertension, which was associated with pressure natriuresis and diuresis. The blood pressure response to l-NAME was attenuated and l-arginine supplementation decreased blood pressure in hydronephrotic animals, but not in the controls. Under control conditions, reactivity and sensitivity of the TGF response were greater in the hydronephrotic group. 7-NI administration increased TGF reactivity and sensitivity in control animals, whereas, in hydronephrotic animals, neuronal NOS (nNOS) inhibition had no effect. l-Arginine attenuated TGF response more in hydronephrotic kidneys than in controls. The hydronephrotic animals displayed various degrees of histopathological changes. ADMA and SDMA levels were higher and the renal expressions of nNOS and endothelial NOS proteins were lower in animals with hydronephrosis. Reduced NO availability in the diseased kidney in hydronephrosis, and subsequent resetting of the TGF mechanism, plays an important role in the development of hypertension.

Cardiovascular and endocrine responses to 90 degree tilt during a 35-day saturation dive to 46 and 37 ATA.

INTRODUCTION: Hyperbaria-induced diuresis is accompanied by decreased basal and stimulated release of arginine vasopressin (AVP) and decreased blood volume possibly contributing to the reported orthostatic intolerance. Since hyperosmolality is not a consistent finding, the explanation of blood volume reduction at hyperbaria must involve an osmotic component to the diuresis. Investigations of a possible involvement of atrial natriuretic peptide (ANP) to the hyperbaric diuresis have revealed mixed results. METHODS: Urinary excretion of electrolytes, AVP, and aidosterone were measured in four male subjects studied at 1 atmosphere absolute (ATA) and at 46 and 37 ATA (0.5 atmospheres pressure O2: 5% N2: remainder He) during a 35-d saturation dive. Also, the supine and 90 degrees tilt-stimulated plasma levels of AVP, plasma renin activity (PRA), and aldosterone, and the suppressed responses of ANP and the cardiovascular responses to tilt were determined at these pressures. RESULTS: Tilt-stimulated levels of PRA were increased two- to threefold and the AVP response was eliminated throughout hyperbaria, except in two episodes of tilt-induced syncope where AVP was elevated 10- to 20-fold. This pattern supports most previous reports. Contrary to some reports, both supine and tilt-suppressed levels of ANP were reduced by about 50% at all three tilt experiments conducted at hyperbaria compared to predive control values. DISCUSSION: These results suggest an altered ANP response at pressures of 37 ATA or greater, which is consistent with an appropriate ANP response to blood volume reduction and further suggest that the hyperbaric diuresis is not dependent on increased ANP.

Urea may regulate urea transporter protein abundance during osmotic diuresis.

Rats with diabetes mellitus have an increase in UT-A1 urea transporter protein abundance and absolute urea excretion, but the relative amount (percentage) of urea in total urinary solute is actually decreased due to the marked glucosuria. Urea-specific signaling pathways have been identified in mIMCD3 cells and renal medulla, suggesting the possibility that changes in the percentage or concentration of urea could be a factor that regulates UT-A1 abundance. In this study, we tested the hypothesis that an increase in a urinary solute other than urea would increase UT-A1 abundance, similar to diabetes mellitus, whereas an increase in urine urea would not. In both inner medullary base and tip, UT-A1 protein abundance increased during NaCl- or glucose-induced osmotic diuresis but not during urea-induced osmotic diuresis. Next, rats undergoing NaCl or glucose diuresis were given supplemental urea to increase the percentage of urine urea to control values. UT-A1 abundance did not increase in these urea-supplemented rats compared with control rats. Additionally, both UT-A2 and UT-B protein abundances in the outer medulla increased during urea-induced osmotic diuresis but not in NaCl or glucose diuresis. We conclude that during osmotic diuresis, UT-A1 abundance increases when the percentage of urea in total urinary solute is low and UT-A2 and UT-B abundances increase when the urea concentration in the medullary interstitium is high. These findings suggest that a reduction in urine or interstitial urea results in an increase in UT-A1 protein abundance in an attempt to restore inner medullary interstitial urea and preserve urine-concentrating ability.

Apelin, a potent diuretic neuropeptide counteracting vasopressin actions through inhibition of vasopressin neuron activity and vasopressin release.

Apelin, a recently isolated neuropeptide that is expressed in the supraoptic and the paraventricular nuclei, acts on specific receptors located on vasopressinergic neurons. The increased phasic pattern of these neurons facilitates sustained antidiuresis during dehydration or lactation. Here, we investigated whether apelin interacts with arginine vasopressin (AVP) to maintain body fluid homeostasis. We first characterized the predominant molecular forms of endogenous hypothalamic and plasma apelin as corresponding to apelin 13 and, to a lesser extent, to apelin 17. We then demonstrated that, in lactating rats, apelin was colocalized with AVP in supraoptic nucleus magnocellular neurons and given intracerebroventricularly inhibited the phasic electrical activity of AVP neurons. In lactating mice, intracerebroventricular administration of apelin 17 reduced plasma AVP levels and increased diuresis. Moreover, water deprivation, which increases systemic AVP release and causes depletion of hypothalamic AVP stores, decreased plasma apelin concentrations and induced hypothalamic accumulation of the peptide, indicating that AVP and apelin are conversely regulated to facilitate systemic AVP release and suppress diuresis. Opposite effects of AVP and apelin are likely to occur at the hypothalamic level through autocrine modulation of the phasic electrical activity of AVP neurons. Altogether, these data demonstrate that apelin acts as a potent diuretic neuropeptide counteracting AVP actions through inhibition of AVP neuron activity and AVP release. The coexistence of apelin and AVP in magnocellular neurons, their opposite biological effects, and regulation are likely to play a key role for maintaining body fluid homeostasis.

An anti-aldosteronic diuretic component (drain dampness) in Polyporus sclerotium.

Polyporus Sclerotium botanically from the Polyporus umbellatus (PERS.) FRIES, was traditionally used for the purpose of promoting diuresis. The present study investigated the diuretic effect of ergosta-4,6,8(14),22-tetraen-3-one (ergone) which is a maker component according to the chemical assay for its quality standardization. It resulted in a reversion to ordinary value of the urinary ratio of Na/K in deoxycoricosterone acetate (DOCA)-treated and adrenalectomized rats, although it had no this effect on the Na or K contents as well as Na/K value both in normal rats and in adrenalectomized rats without DOCA. These data indicate that ergone possesses an anti-aldosteronic diuretic effect. Moreover, it was identified in the blood and bile of rats after its administration to the gastrointestinal tract. The above results demonstrate that it is an active component of Polyporus Sclerotium.

Role of hypothalamic melanocortin 3/4-receptors in mediating chronic cardiovascular, renal, and metabolic actions of leptin.

The present study examined whether blockade of melanocortin receptors subtypes 3 and 4 (MC3/4-R) inhibits chronic cardiovascular and dietary responses to leptin infusion. A cannula was placed in the lateral ventricle of male Sprague-Dawley rats for chronic intracerebroventricular (ICV) infusion via osmotic minipump, and arterial and venous catheters were implanted for measurement of mean arterial pressure (MAP) and heart rate (HR) 24 h/d and IV infusions. After a 5-day control period, rats received (1) 0.9% saline vehicle ICV for 12 days plus leptin (1 microg/kg per minute IV, n=5) during the final 7 days; (2) MC3/4-R antagonist SHU-9119 (1 nmol/h ICV) for 12 days plus leptin (1 microg/kg per minute IV, n=6) during the final 7 days; and (3) SHU-9119 (1 nmol/h ICV, n=8) for 12 days. Leptin infusion in vehicle-treated rats caused a small increase in MAP (5+/-1 mm Hg) despite reduced food intake (23+/-1 to 10+/-1 g/d) and decreased body weight (-6%+/-1%). SHU-9119 infusion completely prevented the cardiovascular and dietary actions of leptin, leading to increased food intake (23+/-1 to 49+/-4 g/d) and body weight (+30%+/-2%), markedly decreased HR (-77+/-9 bpm), and caused a decrease in MAP (-6+/-1 mm Hg). Similar results were observed when SHU-9119 was infused alone in vehicle-treated rats. Leptin decreased plasma insulin to 30% of control values, an effect that was also abolished by SHU-9119 treatment, which caused a 5-fold increase in plasma insulin concentration. Thus, MC3/4-R antagonism completely blocked the chronic cardiovascular, satiety, and metabolic effects of leptin, suggesting that the hypothalamic melanocortin system plays an important role in mediating these actions of leptin.

The effect of drinking tea at high altitude on hydration status and mood.

The effect of drinking tea on hydration status and mood was studied in nine male and four female members of expeditions based at Mt. Everest base camp at an altitude of 5,345 m. Whilst exposed to altitude-cold diuresis, participants were subjected to a crossover experimental design comprising two 24-h dietary interventions. In the "tea" condition, hot brewed tea formed a major part of fluid intake, whereas in the "no-tea" condition tea was excluded from the diet. Subjects were prohibited in both cases from consuming other caffeinated beverages, caffeinated foods, and alcoholic drinks. Mean fluids ingested [mean (SE); tea=3,193 (259) ml versus no tea=3,108 (269) ml] and urine volume (tea=2,686 (276) ml versus no tea=2,625 (342) ml] were similar under both conditions. Statistical analysis found no difference in urine stimulated as a result of the tea intervention (P=0.81). Several markers of hydration status were also taken immediately pre and post each condition, including measures of urine specific gravity, urine electrolyte balance (K+, Na+), and urine colour. None of these measures indicated a difference in hydration status as a result of the dietary intervention in either the control or tea condition. A difference was, however, found in mood, with subjects reporting reduced fatigue when tea was included in the diet (P=0.005). The study shows therefore that even when drunk at high altitude where fluid balance is stressed, there is no evidence that tea acts as a diuretic when consumed through natural routes of ingestion by regular tea drinkers, but that it does have a positive effect on mood.

Effects of Helichrysum ceres extracts on renal function and blood pressure in the rat.

OBJECTIVE: To evaluate the effects of Helicrysum ceres root and leaf extracts on mean arterial blood pressure and renal fluid and electrolyte handling in anesthetized male Sprague-Dawley rats. DESIGN: Cross sectional study. SETTING: Departments of Physiology and Pharmacy, University of Zimbabwe. SUBJECTS: Eight separate groups comprising of control and treated Male Sprague-Dawley rats (n =6 in each group) were anesthetized and placed on a continuous jugular infusion of 0.077 M NaCl at 150 microL min(-1). The left carotid artery was cannulated with polythene tubing and then connected to a pressure transducer for blood pressure measurements. After 3 h equilibration period, consecutive 20 min urine collections and blood pressure measurements were made over the subsequent 4 h of 1 h 20 min control, 1 h treatment and I h 40 min post-equilibration periods for measurements of urine flow and Na+ and K+ excretion rates. Helichrysum ceres leaf extracts at 0.3, 0.6 and 1.2 microg min(-1) roots 0.3, 3 and 6 microg min(-1) were added to the infusate during the treatment period. To establish whether the extracts had activities comparable to drugs already in use, a separate group of animals was administered furosemide (0.12 microg min(-1)) during the treatment period. MAIN OUTCOME MEASURES: Hypotension, Natriuresis and Diuresis. RESULTS: Infusion of graded doses of aqueous leaf extracts of Helicrysum ceres provoked an increase in urine flow rates but did not achieve statistical significance. However, the extracts produced dose dependent decrease in potassium excretion as well as increases in urinary Na+ outputs and diuresis. Administration of the various doses of aqueous root extracts of Helicrysum ceres significantly increased urine flow rate and urinary Na+ excretion in all groups. The intravenous (i.v.) administration of the aqueous root or leaf extracts of Helichrysum ceres significantly depressed mean arterial blood pressure (MAP). The diuretic and natriuretic effects of plant extracts were not significantly different to that of furosemide. CONCLUSION: The results suggest that oral administration to rats of aqueous crude Helicrysum ceres root or leaves extracts induce hypotension and natriuresis.

Diuretic effect and mechanism of action of parsley.

This work provides substantial evidence for the advocated diuretic effect of parsley in folk medicine and determines the mechanism of action of the herb. Rats offered an aqueous parsley seed extract to drink, eliminated a significantly larger volume of urine per 24 h as compared to when they were drinking water. These findings were supported by the results of other experiments using an in situ kidney perfusion technique which demonstrated also a significant increase in urine flow rate with parsley seed extract. This effect was still apparent in presence of amiloride, furosemide and in the absence of sodium, but not in the absence of potassium, suggesting that the diuretic effect of the herb is mediated through an increase in K+ retention in the lumen. Parsley extract, was shown on the other hand, to reduce the activity of the Na+-K+ ATPase in both cortex and medulla homogenates. Such an inhibition would decrease apical cellular Na+ reabsorption, lower K+ secretion, increase K+ concentration in the intercellular space and consequently would inhibit passive K+ influx across the tight junctions. The mechanism of action of parsley seems to be mediated through an inhibition of the Na+-K+ pump that would lead to a reduction in Na+ and K+ reabsorption leading thus to an osmotic water flow into the lumen, and diuresis.

[Enhancing efficiency of sanatorium treatment of patients with chronic pyelonephritis using hyperbaric oxygenation]. / Pidvyshchennia efektyvnosti sanatorno-kurortnoho likuvannia khvorykh na khronichnyi piielonefryt za dopomohoiu hiperbarychnoï oksyhenatsiï.

Clinical studies were made in 117 patients with chronic pyelonephritis at the stage of sanatorium-and-health-resort treatment using hyperbaric oxygenation. Supplementing the "traditional" naftusya-based balneotherapy with hyperbaric oxygenation has been shown to potentiate the effect of the water on the course of the illness, functional condition of the urinary organs, to strengthen the potential of those systems res responsible for homeostasis of the peroxide oxygenation of lipids in the body, which fact validates a high efficiency of their combined use.

Effect of crude extract of Stevia rebaudiana on renal water and electrolytes excretion.

To evaluate the effect of crude extract of Stevia rebaudiana on renal water, Na+ and K+ excretion, male Wistar rats (250-350 g each) under antidiuresis or water diuresis conditions, were evaluated. During intravenous infusion of the extract (0.05 mg/min/100 g) no significant differences were detected in mean arterial pressure or renal hemodynamics parameters. In contrast, fractional water and sodium excretion and solute clearance increased significantly, in both groups of animals. In antidiuresis rats the extract significantly increased reabsorption of water by the collecting duct and in water diuresis animals the extract significantly increased free water clearance. The data suggest preferential action of the extract in the proximal tubular cells involved with salt transport mechanism.