Association between urinary indicators of renal dysfunction and metal concentrations in workers chronically co-exposed to cadmium,zinc and lead

The study was carried out in 31 workers co-exposed to cadmium, lead and zinc fumes and dusts in a zinc ore refinery. Urinary cadmium, lead, zinc, β₂-M levels and NAG activities were determined to evaluate the possible dose-effect relationship between these parameters. A correlation was found between urinary cadmium, lead and zinc concentrations, and urinary β₂-M levels and NAG activities of the exposed group. A statistically significant increase was also observed for urinary NAG activity in exposed workers who had urinary cadmium concentrations > 2 μg g^?1 creatinine. However, in the same exposed group, the increment of β₂-M was not statistically significant. In conclusion, the present study thus confirms the earlier observations and may suggest the notion that the urinary NAG seems to be a more sensitive indicator than urinary β₂-M level in early stages of renal injury of moderately cadmium co-exposure with lead and zinc even at urinary cadmium concentration as low as 2 μg g^?1 creatinine. When the earlier studies on the irreversibility of cadmium-induced tubular dysfunction and the present results were taken into consideration, the present health-based biological limit proposed by the WHO (5 μg g^?1 creatinine) seems to be high for the occupational exposure to cadmium.     

大鼠尿中酶类参考值检测

目的调查正常大鼠尿液样本中酶类参考值范围。方法采集95只正常SD大鼠的4 h尿液,用生化仪检测尿液中的N-乙酰基-β-D氨基葡萄糖酶（NAG）、碱性磷酸酶（ALP）、谷氨酰氨基转移酶（γ-GT）和乳酸脱氢酶（LDH）的值,参考范围以95%百分位上界表示。结果参考值范围为,雌性：NAG〈5.3 U/L,ALP〈110.8 U/L,γ-GT〈753.0 U/L,LDH〈32.6 U/L;雄性：NAG〈27.3 U/L,ALP〈329.0 U/L,γ-GT〈769.8 U/L,LDH〈40.0 U/L。以/g Cre为单位的参考值范围,雌性：NAG〈28.9 U/g,ALP〈723.5 U/g,γ-GT〈1763.2 U/g,LDH〈113.1 U/g;雄性：NAG〈84.3 U/g,ALP〈680.2 U/g,γ-GT〈2522.3 U/g,LDH〈121.8 U/g。结论尿中酶类参考值范围为药物肾毒性评价提供了背景数据。     

Lithium-induced renal toxicity in rats: Protection by a novel antioxidant caffeic acid phenethyl ester

Lithium carbonate used in the long-term treatment of manic-depressive illness has been reported to lead to progressive renal impairment in rats and humans. Caffeic acid phenethyl ester (CAPE), a component of honeybee propolis, protects tissues from reactive oxygene species mediated oxidative stress in ischemia-reperfusion and toxic injuries. The beneficial effect CAPE on lithium-induced nephrotoxicity has not been reported yet. The purpose of this study was to examine a possible renoprotective effect of CAPE against lithium-induced nephrotoxicity in a rat model. Twenty-two adult male rats were randomly divided into three experimental groups, as follows: control group, lithium-treated group (Li), and lithium plus CAPE-treated group (Li+CAPE). Li were treated intraperitoneally (i.p.) with 25 mg/kg Li₂CO₃ solution in 0.9% NaCl twice daily for 4 weeks. CAPE was co-administered i.p. with a dose of 10 μM/kg/day for 4 weeks. Serum Li, blood urea nitrogen and plasma creatinine, urinary N-acetyl-β-D-glucosaminidase (NAG, a marker of renal tubular injury), and malondialdehyde (MDA, an index of lipid peroxidation), were used as markers of oxidative stress-induced renal impairment in Li-treated rats. Superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities were studied to evaluate the changes of antioxidant status in renal tissue. Serum Li levels were found high in the Li and Li+CAPE groups. In Li-administrated rats, urinary NAG and renal MDA levels were increased according to control and Li+CAPE groups (p < 0.05). CAPE caused a significant reduction in the levels of these parameters. Likewise, renal SOD, CAT and GSH-Px activities were decreased in Li-administrated animals; CAPE caused a significant increase in the activities of these antioxidant enzymes. In conclusion, CAPE treatment has a protective effect against Li-induced renal tubular damage and oxidative stress in a rat model.     

Influence of feeding schedules on the chronobiology of renin activity,urinary electrolytes and blood pressure in dogs

The contribution of the renin–angiotensin–aldosterone system (RAAS) to the development of congestive heart failure (CHF) and hypertension (HT) has long been recognized. Medications that are commonly used in the course of CHF and HT are most often given with morning food for the sake of convenience and therapeutic compliance. However, biological rhythms and their responsiveness to environmental clues such as food intake may noticeably impact the effectiveness of drugs used in the management of cardiovascular disorders. Only sparse information about the effect of feeding schedules on the biology of the RAAS and blood pressure (BP) is presently available. Two studies were designed to explore the chronobiology of renin activity (RA), BP, renal sodium (U_Na,fe) and potassium (U_K,fe) handling in relation to meal timing in dogs. In a first experiment (Study a), blood and urinary samples for measurement of RA, U_Na,fe and U_K,fe were drawn from 18 healthy beagle dogs fed a normal-sodium diet at either 07:00, 13:00 or 19:00?h. In a second experiment (Study b), BP was recorded continuously from six healthy, telemetered beagle dogs fed a similar diet at 07:00, or 19:00?h. Data were collected throughout 24-h time periods, and analyzed by means of nonlinear mixed-effects models. Differences between the geometric means of early versus late time after feeding observations were further compared using parametric statistics. In agreement with our previous investigations, the results indicate that RA, U_Na,fe, U_K,fe, systolic, and diastolic BP oscillate with a circadian periodicity in dogs fed a regular diet at 07:00?h. A cosine model with a fixed 24-h period was found to fit the variations of RA, U_K,fe and BP well, whereas cyclic changes in U_Na,fe were best characterized by means of a combined cosine and surge model, reflecting a postprandial sodium excretion followed by a monotonous decay. Our data show that feeding time has a marked influence on the chronobiology of the renin cascade, urinary electrolytes, and BP. Introducing a 6- or 12-h delay in the dogs’ feeding schedule caused a shift of similar magnitude (05:06 and 12:32?h for Studies a and b, respectively) in the rhythm of these biomarkers. In all study groups, RA and BP exhibited a marked fall just after food intake. The drop in RA is consistent with sodium and water-induced body fluid expansion, while the reduction of BP could be related to the decreased activity of renin and the secretion of vasodilatory gut peptides. An approximately 1.5-fold (1.2–1.6-fold) change between the average early and late time after feeding observations was found for RA (p?<?0.0001), U_Na,fe (p?<?0.01) and U_K,fe (p?<?0.05). Postprandial variations in BP, albeit small (ca. 10?mmHg), were statistically significant (p?<?0.01) and supported by the model-based analysis.

In conclusion, the timing of food intake appears to be pivotal to the circadian organization of the renin cascade and BP. This synchronizing effect could be mediated by feeding-related signals, such as dietary sodium, capable of entraining circadian oscillators downstream of the master, light–dark-adjusted pacemaker in the suprachiasmatic nucleus.     

Hepatoprotective effects of phosphatidylserine liposomes on carbon tetrachloride-induced hepatotoxicity in rats

It has been proposed carbon tetrachloride (CCl₄) intoxication due to the production of free radicals and serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) overload results hepatotoxicity. Phosphatidylserine (PS) has shown antioxidant activity in numerous studies. Therefore, this study was aimed to investigate the effects of PS liposomes treatment against the CCl₄-induced hepatotoxicity in a rat model. Male Wistar rats were treated with PS (10 mg/kg, oral) or phosphatidylcholine liposomes (PC) (10 mg/kg, oral) for 3 days before CCl₄ (2 ml/kg; ip once on the third day) injection. The serum level of ALT, AST, and ALP were measured. Also, antioxidant assays were performed. Administration of PS with CCl₄ significantly inhibited alterations in the serum levels of AST, ALP (^**P < 0.01), and ALT (^***P < 0.001) compared with control group. Furthermore, measurement of malondialdehyde (MDA), catalase (CAT), and superoxide dismutase (SOD) levels indicated that PS significantly reduced reactive oxygen species. The results of the present study showed the hepatoprotective effects of PS against CCl₄-induced hepatotoxicity in rats.     

Chronobiology of the renin-angiotensin-aldosterone system in dogs: relation to blood pressure and renal physiology

The renin-angiotensin-aldosterone system (RAAS) plays a pivotal role in the regulation of blood pressure and volume homeostasis. Its contribution to the development of cardiovascular diseases has long been recognized. Extensive literature has shown that peptides of the RAAS oscillate with a circadian periodicity in humans, under strong influence of posture, sleep, and age. Although observations of time-variant changes in the renin cascade are available in dogs, no detailed chronobiological investigation has been conducted so far. The present studies were designed to explore the circadian variations of plasma renin activity (RA) and urinary aldosterone-to-creatinine ratio (U_A:C) in relation to blood pressure (BP), sodium (U_Na, U_Na,fe), and potassium (U_K, U_K,fe) renal handling. Data derived from intensive blood and urine sampling, as well as continuous BP monitoring, were collected throughout a 24-h time period, and analyzed by means of nonlinear mixed-effects models. Differences between the geometric means of day and night observations were compared by parametric statistics. Our results show that variables of the renin cascade, BP, and urinary electrolytes oscillate with significant day-night differences in dogs. An approximately 2-fold (1.6–3.2-fold) change between the average day and night measurements was found for RA (p?<?0.001), U_A:C (p?=?0.01), U_K,fe (p?=?0.01), and U_Na (p?=?0.007). Circadian variations in BP, albeit small (less than 10?mm Hg), were statistically significant (p?<?0.01) and supported by the model-based analysis. For all variables but U_Na and U_Na,fe, the levels were higher at night than during the day. The data also indicate that blood pressure oscillates in parallel to the RAAS, such that, as opposed to healthy humans, BP does not drop at night in dogs. The postprandial decrease in RA is assumed to be related to body fluid volume expansion secondary to water and sodium intake, whereas the reduction of U_A:C reflects aldosterone-stimulated secretion by the renin-angiotensin II pathway. U_Na and U_Na,fe peaked in the afternoon, about 7–8?h after food intake, which is consistent with the “impulse-response pattern” of sodium excretion described in previous publications. Finally, U_K and U_K,fe mirrored aldosterone-mediated potassium secretion in the kidney tubules. To describe the circadian variations of the various variables, two different mathematical representations were applied. A cosine model with a fixed 24-h period was found to fit the periodic variations of RA, U_A:C, U_K, U_K,fe, and BP well, whereas changes in U_Na and U_Na,fe were best characterized by a surge model. The use of nonlinear mixed effects allowed estimation of population characteristics that can influence the periodicity of the RAAS. Specifically, sodium intake was found to interact with the tonic and the phasic secretion of renin, suggesting that varying feeding time could also impact the chronobiology of the renin cascade. (Author correspondence: jonathan.mochel@novartis.com)     

Carbonic anhydrase in Ranunculus penicillatus spp. pseudofluitans: activity, location and implications for carbon assimilation

Levels of carbonic anhydrase activity were determined on a total (60 E_Umg^?1 protein), external (7.36 E_U), internal (50.14 E_U) and protoplast (15.63 E_U) basis for Ranunculus penicillatus (Dumort.) Bab ssp. pseudofluitans (Syme) S. Webster, a freshwater aquatic macrophyte, by conventional electrometric methods. The site of activity of ‘external’ carbonic anhydrase (CA) has been visualized using 5-Dimethylaminonapthalene-1- sulphonamide (DNSA)-CA fluorescent complex formation, and is postulated to be closely associated with the epidermal cell wall. The photosynthetic rate of R. penicillatus ssp. pseudofluitans at pH 9.0 is in excess of the uncatalysed rate of production of CO₂ from HCO^?₃, and this plant is therefore using HCO^?₃ for photosynthesis. The possible contribution of CA activity to inorganic carbon assimilation, and specifically to transport of HCO^?₃, in submerged aquatic plants is discussed.     

Increased urinary zinc excretion in cancer patients is linked to immune activation and renal tubular cell dysfunction

Urinary zinc excretion is known to be increased in cancer patients, but the pathogenesis of this phenomenon remains uncertain. Both skeletal muscle catabolism and renal tubular cell dysfunction have been proposed to explain this observation. We have investigated urinary zinc and N-acetyl--d-glucosaminidase (NAG), an indicator of renal tubular cell dysfunction, as well as serum neopterin, an index of systemic immune activation, in 22 patients with cancer and seven controls. Both serum neopterin and urinary zinc were significantly elevated in cancer patients (15.8 ± 12.7 versus 7.3 ± 2.3 nmol l^–1 and 1.77 ± 0.80 versus 1.21 ± 0.41 mmol mol^–1 creatinine, P < 0 and P < 0.05, respectively), while NAG was similar in cancer patients and the controls (13.58 ± 13.80 versus 13.68 ± 12.19 kat mol^–1 creatinine). A significant correlation was observed between serum neopterin and urine zinc (rs = 0.5119, P < 0.02), serum neopterin and urine NAG (rs = 0.6761, P < 0.002), and urinary zinc and NAG (rs = 0.6348, P < 0.002). In conclusion, the present data indicate a link between urinary zinc excretion and immune activation as well as renal tubular cell dysfunction. In addition, renal tubular cell dysfunction appears to be linked to immune activation.     

A novel antioxidant agent caffeic acid phenethyl ester prevents long-term mobile phone exposure-induced renal impairment in rat

Caffeic acid phenethyl ester (CAPE), a flavonoid like compound, is one of the major components of honeybee propolis. It has been used in folk medicine for many years in Middle East countries. It was found to be a potent free radical scavenger and antioxidant recently. The aim of this study was to examine long-term applied 900 MHz emitting mobile phone-induced oxidative stress that promotes production of reactive oxygen species (ROS) and, was to investigate the role of CAPE on kidney tissue against the possible electromagnetic radiation (EMR)-induced renal impairment in rats. In particular, the ROS such as superoxide and nitric oxide (NO) may contribute to the pathophysiology of EMR-induced renal impairment. Malondialdehyde (MDA, an index of lipid peroxidation) levels, urinary N-acetyl-β-d-glucosaminidase (NAG, a marker of renal tubular injury) and nitric oxide (NO, an oxidant product) levels were used as markers of oxidative stress-induced renal impairment and the success of CAPE treatment. The activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) in renal tissue were determined to evaluate the changes of antioxidant status. The rats used in the study were randomly grouped (10 each) as follows: i) Control group (without stress and EMR), ii) Sham-operated rats stayed without exposure to EMR (exposure device off), iii) Rats exposed to 900 MHz EMR (EMR group), and iv) A 900 MHz EMR exposed + CAPE treated group (EMR + CAPE group). In the EMR exposed group, while tissue MDA, NO levels and urinary NAG levels increased (p < 0.0001), the activities of SOD, CAT, and GSH-Px in renal tissue were reduced (p < 0.001). CAPE treatment reversed these effects as well (p < 0.0001, p < 0.001 respectively). In conclusion, the increase in NO and MDA levels of renal tissue, and in urinary NAG with the decrease in renal SOD, CAT, GSH-Px activities demonstrate the role of oxidative mechanisms in 900 MHz mobile phone-induced renal tissue damage, and CAPE, via its free radical scavenging and antioxidant properties, ameliorates oxidative renal damage. These results strongly suggest that CAPE exhibits a protective effect on mobile phone-induced and free radical mediated oxidative renal impairment in rats.     

Age related changes of N-acetyl-beta-D-glucosaminidase and L-alanine aminopeptidase in mouse kidney, urine and plasma

Age and sex dependent differences of N-acetyl-beta-D-glucosaminidase (NAG) and L-alanine aminopeptidase (AAP) activities in kidney, urine and plasma of male and female mice were studied. The sex difference in NAG activity appeared between 27 and 38 days of age with the manifestation of significant differences in body weight and kidney growth. NAG activity in male kidneys was 3-fold that in females and its urinary level in mature males was over 10-fold higher. Androgenic regulation was found not only in the NAG contents in the kidneys and in the urinary excretion but also in the plasma NAG level, which showed higher in females. On the other hand, AAP activity in kidney, urine and plasma did not show much sex differences. Age related changes in AAP activity were not found except in the kidney and marked androgenic regulation was also not found in AAP. These results indicate that NAG and AAP, which are both urinary enzymes used as indicators of renal lesions, may be regulated differently.     

Effect of polyaspartic acid on CdCl2-induced nephrotoxicity in the rat

We produced an animal model of CdCl₂ nephrotoxicity in rats, and treated them with polyaspartic acid (PAA) to prevent renal damage. Male Sprague-Dawley (SD) rats (190–200 g) were used to induce proximal renal tubular damage by daily injection of CdCl₂ 3.0 mg/1,000 g body wt for 2 wk. CdCl₂-exposed SD rats exhibited significant increases in urine volume, urinary excretion ofN-acetyl-β-D-glucosaminidase (NAG), alanine aminopeptidase (AAP), and fractional excretion of sodium (FENa) and a decrease in the percentage of tubular reabsorption of phosphate (%TRP). Of these indicators of proximal tubular function, AAP and %TRP are more sensitive than NAG or FENa. No glycosuria or aminoaciduria, however, were observed. PAA markedly improved these indicators of proximal tubular function. Daily urinary protein excretion and creatinine clearance, on the other hand, did not change after administration of PAA. Cd concentrations in the cortex were 3 times higher than in the medulla, however, there were no differences between Cd-treated rats and PAA-treated rats. Our animal model is an excellent one for determining the effect of cadmium on renal proximal tubule damage. PAA appears to be useful in the treatment of CdCl₂ nephrotoxicity.     

Hepatoprotective potential of new steroid against carbon tetrachloride-induced hepatic injury

The present study was designed to evaluate the hepatoprotective effects of newly isolated stigmast-4, 20 (21), 23-trien-3-one (STO) against carbon tetrachloride-induced hepatic injury in Wistar albino rats. Hepatotoxicity was induced by the administration of a single intraperitoneal dose of CCl₄ (0.5 mL/kg CCl₄ in olive oil) in experimental rats. Three different doses (2.5, 5.0, and 10 mg/kg, p.o) of STO was administered to the test groups during whole experimental protocol. Changes in the activity of serum ALT, AST, ALP, TB, and TP, anti-oxidant enzymes like SOD, CAT, GPx, GST, and LPO were studied in CCl₄-induced hepatocellular carcinogenesis. The altered levels of serum ALT, AST, ALP, TB, and TP restored toward normalization significantly by STO in a dose dependant manner. The biochemical observations were supplemented with histopathological examination of rat liver sections. Meanwhile, it also produced a significant and dose-dependent reversal of CCl₄-diminished activity of anti-oxidant enzymes like SOD, CAT, GPx, GST, and the reduced CCl₄-elevated level of LPO. STO significantly prevented the increased levels of serum markers, also suppressed the free radical processes by scavenging hydroxyl radicals. It also modulates the levels of LPO and markedly increases the endogenous anti-oxidant enzymes level in CCl₄-induced hepatic injury.     

Oral administration of sodium selenite minimizes cisplatin toxicity on proximal tubules of rats

Cisplatin (c-DDP) is a widely used antineoplastic drug whose main side effect is nephrotoxicity. Selenium, administered intravenously or intraperitoneally, has been shown to provided protection against c-DDP-induced nephrotoxicity in rats. In the present study, the protective effect of orally administered sodium selenite on c-DDP toxicity was further examined. Animals treated with c-DDP alone showed increased urinary volume, decreased creatinine clearance (GFR), and a rise in urinary N-acetyl-(β-d-glucosaminidase) (NAG) isoenzyme B activity. When sodium selenite was given prior to c-DDP, rats showed less GFR decline, delayed urinary volume increases, and no urinary NAG isoenzyme B activity increment. It is suggested that a single oral dose of sodium selenite given prior to c-DDP administration, although not preventing deterioration of renal function, partially protects rats from early proximal tubular injury.     

Methodological considerations with the use of urine samples for assessment of mercury excretion and markers of renal damage

Objective:?To provide recommendations for design and analysis of studies using urine specimens to evaluate renal function or mercury excretion in children.

Methods:?An analysis of mercury, albumin, γ-glutamyl transpeptidase (γ-GT) and N-acetyl-β-D-glucosaminidase (NAG) concentrations was carried out.

Results:?Mercury concentration and creatinine-corrected renal markers were higher in daytime compared with overnight samples. Excretion rates increased with urinary flow rate. γ-GT and NAG concentrations decreased with storage time at ?20°C. Differences by age, sex and race were noted.

Conclusions:?We recommend use of these creatinine-corrected markers and collection of timed overnight urine samples, stored at ?70°C, with control for urinary flow rate, age, sex and race in statistical models.     

CO2浓度升高、增温和冬小麦种植对土壤酶活性的影响

研究农田土壤酶活性对CO₂浓度升高和增温的响应,可为气候变化背景下农田生态系统养分管理提供科学依据。本研究在人工模拟气候室进行盆栽控制试验,设置了4种气候情景,分别为对照(CK,CO₂浓度400 μmol·mol^-1+正常环境温度)、CO₂浓度升高(ECO₂,CO₂浓度800 μmol·mol^-1+正常环境温度)、增温(ET,CO₂浓度400 μmol·mol^-1+增温4 ℃)及CO₂浓度和温度均升高(ECO₂+T,CO₂浓度800 μmol·mol^-1+增温4 ℃),研究有、无冬小麦生长下β--葡萄糖苷酶(βG)、β-N-乙酰葡糖苷酶(NAG)、碱性磷酸单脂酶(ALP)和多酚氧化酶(PPO)4种土壤酶活性在冬小麦拔节期(JS)、开花期(AS)、灌浆期(FS)和成熟期(MS)对CO₂浓度升高和增温的响应。结果表明:无冬小麦生长下,ECO₂与CK间4种土壤酶活性差异不显著,而ET和ECO₂+T处理对4种土壤酶活性有显著抑制作用。有冬小麦生长条件下,与CK相比,ECO₂和ECO₂+T处理对4种土壤酶活性均无显著影响;ET处理对土壤ALP和PPO活性有显著影响;ECO₂+T与ET间4种土壤酶活性有显著差异,与ET相比,ECO₂+T处理的土壤βG活性在JS期显著增加,NAG活性在JS期显著降低,ALP活性在AS和FS期显著增加,PPO活性在JS期显著降低,而在AS期显著增加。CO₂浓度升高与增温的交互作用在有、无冬小麦生长下均对土壤NAG和ALP活性有显著影响;无冬小麦生长下,增温和试验时段的交互作用对4种土壤酶活性有显著影响,而在有冬小麦生长下,增温和生育期的交互作用仅对ALP和PPO活性有显著影响;CO₂浓度升高、增温与试验时段的交互作用在无冬小麦生长下对土壤βG、ALP和PPO活性有显著影响,而在有冬小麦生长下CO₂浓度升高、增温与生育期对土壤NAG、ALP和PPO活性有显著影响。冬小麦生长对土壤βG、NAG和ALP活性在前两个生育期(JS+AS期)表现为显著抑制作用,在后两个生育期(FS+MS期)表现为显著促进作用,对土壤PPO活性在全生育期均表现为显著抑制作用。总体上,CO₂浓度升高对冬小麦土壤酶活性的影响不显著,而CO₂浓度与温度均升高对冬小麦土壤酶活性的影响在不同生育期因土壤酶种类不同而不同;此外,有、无冬小麦条件下4种土壤酶活性对CO₂浓度升高与增温的交互作用响应程度不一。     

Estimation of the reference level of urinary cadmium by using hybrid method in cadmium-polluted and non-polluted areas in China

This study investigated the reference level of urinary cadmium (UCd) of two Cd-polluted areas and one non-polluted area in China by applying the updated hybrid approach. Urinary N-acetyl-β-d-glucosaminidase (NAG) and β-2-microglobulin (β₂MG) were considered as indicators of early renal dysfunction. UCd was regarded as an indicator of the total internal Cd exposure. We recruited 3285 inhabitants for this investigation. Among them, 2106 were from polluted areas, while the other 1179 were from non-polluted areas. BMDL₁₀ (the lower 95% confidence limit of the benchmark dose (BMD)) of UCd for NAG was 1.55 μg/g creatine in men and 1.59 μg/g creatine in women. Using β₂MG as the renal effect marker, BMDL₁₀ of UCd was 1.58 μg/g and 1.53 μg/g in men and women, respectively. Our BMDL estimates accounting for age were lower than those reported in previous studies, suggesting that policies to control Cd exposure are warranted.     

CISPLATIN-INDUCED VOMITING DEPENDS ON CIRCADIAN TIMING

We examined whether the clock time of cisplatin plus antiemetic and diuretic administration affects the amount of cisplatin-associated emesis and severity of renal toxicity. We treated 22 patients with urogenital cancer with two courses of chemotherapy containing 70 mg/m² of cisplatin. Cisplatin together with furosemide was administered in the morning (05:00) or evening (17:00) during two courses 1 month apart in a crossover fashion. Ondansetron was given either before or after cisplatin to control nausea and vomiting. The number of vomiting episodes, serum creatinine, serum urea nitrogen (BUN), creatinine clearance, and urinary β-N-acetyl glucosamidase (NAG) concentration were evaluated before and after each treatment course. Regardless of the timing of ondansetron, morning compared to evening cisplatin was always associated with greater vomiting in the first treatment course. However, prophylactic administration of ondansetron markedly diminished the impact of the clock time of cisplatin administration. Serum creatinine transiently decreased rather than increased 14 days after cisplatin and furosemide administration, while NAG excretion increased 3 days after cisplatin and furosemide administration. In the first course, serum creatinine levels were similar regardless of the clock time of cisplatin and furosemide administration. However, in the second course, serum creatinine rose in patients given evening cisplatin and furosemide, while it remained unchanged in those given morning cisplatin and furosemide. Moreover, the first course morning cisplatin and furosemide treatment was associated with less change in NAG excretion (less kidney toxicity) than the first course of evening cisplatin and furosemide treatment. The second course evening cisplatin and furosemide treatment was associated with an increase in NAG excretion compared to the first course of treatment, while morning cisplatin and furosemide treatment in the second course showed less change in NAG excretion compared to the first course. The clock time of cisplatin administration had an impact on the frequency of emesis. Prophylactic ondansetron, however, diminished the time-of-day dependency of cisplatin-induced vomiting. Administration of cisplatin and furosemide in the morning rather than evening appears to cause less renal damage, and this damage may be further reduced with aggressive hydration and routine administration of furosemide. (Chronobiology International, 18(5), 851–863, 2001)     

Turnover of labile and recalcitrant soil carbon differ in response to nitrate and ammonium deposition in an ombrotrophic peatland

The effects of 4 years of simulated nitrogen deposition, as nitrate (NO₃^?) and ammonium (NH₄⁺), on microbial carbon turnover were studied in an ombrotrophic peatland. We investigated the mineralization of simple forms of carbon using MicroResp^? measurements (a multiple substrate induced respiration technique) and the activities of four soil enzymes involved in the decomposition of more complex forms of carbon or in nutrient acquisition: N‐acetyl‐glucosaminidase (NAG), cellobiohydrolase (CBH), acid phosphatase (AP), and phenol oxidase (PO). The potential mineralization of labile forms of carbon was significantly enhanced at the higher N additions, especially with NH₄⁺ amendments, while potential enzyme activities involved in breakdown of more complex forms of carbon or nutrient acquisition decreased slightly (NAG and CBH) or remained unchanged (AP and PO) with N amendments. This study also showed the importance of distinguishing between NO₃^? and NH₄⁺ amendments, as their impact often differed. It is possible that the limited response on potential extracellular enzyme activity is due to other factors, such as limited exposure to the added N in the deeper soil or continued suboptimal functioning of the enzymes due to the low pH, possibly via the inhibitory effect of low phenol oxidase activity.     

Heat acclimation causes some alterations in serum enzymes activities in streptozotocin-diabetic rats

The present study investigated the effect of long-term heat acclimation and experimental diabetes on serum activity of transaminases (AST, ALT), ALP, LDH and elastase complex, as well as blood glucose and HbA1c level in Wistar rats. The heat acclimation model was established with the artificial heat chamber (35±1 °C and 30-40% humidity) for a period of 28 days, while the control groups were held on 20±2 °C. Experimental diabetes was induced by single streptozotocine (STZ) injection (55 mg/kg bodyweight) The changes caused by insulin treatment (2 IU/100 g body weight, 14 days, twice daily) in both thermal groups were also investigated.STZ-diabetes leads to significant increase in blood glucose and HbA1c level, AST, ALT and ALP activities in both thermal groups (normothermic and heat acclimated), decrease in LDH activity in normothermic animals and increase in heat-acclimated ones. Treatment with insulin restores the blood glucose, HbA1c and enzymes activities regardless of the previous thermal exposure.Prolonged acclimation of control animals to elevated ambient temperature resulted in significant decrease in blood glucose level, AST, ALT, ALP and LDH activities and non-significant changes in HbA1c. Compared to diabetic rats from room temperature, heat-acclimated diabetic ones have significantly higher blood glucose, AST, ALP and LDH activity, lower HbA1c concentration and no significant changes in ALT. Most of the changes observed in heat-acclimated insulin-treated diabetic rats did not significantly differ compared to those from room temperature.The overall two-way ANOVA analyses showed that diabetic state causes significant changes in the blood glucose, HbA1c, AST, ALT and ALP activity, while heat acclimation causes significant changes only in HbA1c level and AST activity. Both of the factors (diabetic state and heat acclimation) have significant common effects on AST, ALP and LDH activity.     

Human parathyroid hormone (1-34) increases urinary excretion of lysosomal enzymes in rats

The kidney is the major target of parathyroid hormone (PTH), and PTH influences the urinary excretion of calcium, phosphate and hydrogen ions. It was previously reported that the urinary, excretion of N-acetyl-beta-D-glucosaminidase (NAG), a lysosomal enzyme, transiently increases after human PTH (hPTH) (1-34) infusion in normal subjects and idiopathic hypoparathyroidism patients, but not in pseudohypoparathyroidism type I patients. Here we report that intravenous infusion of hPTH(1-34) to rats transiently increased the urinary excretion of various lysosomal enzymes, such as beta-glucuronidase and acid phosphatase as well as NAG. However, it did not affect the urinary excretion of tubular brush border membrane enzymes, i.e. alkaline phosphatase, leucine aminopeptidase and gamma-glutamyl transpeptidase. Human PTH(1-34) dose-dependently increased the urinary excretion of NAG in rats with a peak at 30 min, which returned to a baseline within 60 min. The increase in the urinary NAG excretion caused by hPTH(1-34) positively correlated with the increase in the urinary cAMP excretion (r = 0.844, p < 0.01), and infusion of dibutyryl cAMP at a dose of 20 mg/kg similarly increased the urinary excretion of NAG. These results suggested that the increase in the urinary excretion of lysosomal enzymes caused by hPTH(1-34) may be a functional response to hPTH(1-34) occurring in the renal tubules via PTH signaling pathway.