Metabolic and volume status evaluation of hemodialysis patients with and without residual renal function in the long interdialytic interval / Avaliação metabólica e volêmica no maior intervalo interdialítico de pacientes em hemodiálise com e sem função renal residual

Abstract Introduction: It is unclear whether residual renal function (RRF) in dialysis patients can attenuate the metabolic impact of the long 68-hour interdialytic interval, in which water, acid, and electrolyte accumulation occurs. Objective: to evaluate serum electrolyte levels, water balance, and acid-base status in dialytic patients with and without RRF over the long interdialytic interval (LII). Methodology: this was a single-center, cross-sectional, and analytical study that compared patients with and without RRF, defined by diuresis above 200 mL in 24 hours. Patients were weighed and serum samples were collected for biochemical and gasometric analysis at the beginning and at the end of the LII. Results: 27 and 24 patients with and without RRF were evaluated, respectively. Patients without RRF had a higher increase in serum potassium during the LII (2.67 x 1.14 mEq/L, p < 0.001), reaching higher values at the end of the study (6.8 x 5.72 mEq/L, p < 0.001) and lower pH value at the beginning of the interval (7.40 x 7.43, p = 0.018). More patients with serum bicarbonate < 18 mEq/L (50 x 14.8%, p = 0.007) and mixed acid-base disorder (57.7 x 29.2%, p = 0.042), as well as greater interdialytic weight gain (14.67 x 8.87 mL/kg/h, p < 0.001) and lower natremia (137 x 139 mEq/L, p = 0.02) at the end of the interval. Calcemia and phosphatemia were not different between the groups. Conclusion: Patients with RRF had better control of serum potassium, sodium, acid-base status, and volemia throughout the LII.

Resumo Introdução: Não se sabe ao certo se a função renal residual (FRR) de pacientes dialíticos pode atenuar o impacto metabólico do maior intervalo interdialítico (MII) de 68 horas, no qual ocorre acúmulo de volume, ácidos e eletrólitos. Objetivo: Avaliar os níveis séricos de eletrólitos, balanço hídrico e status ácido-básico de pacientes dialíticos com e sem FRR ao longo do MII. Metodologia: Tratou-se de estudo unicêntrico, transversal e analítico, que comparou pacientes com e sem FRR, definida como diurese acima de 200 mL em 24 horas. Para tal, os pacientes foram pesados e submetidos à coleta de amostras séricas para análise bioquímica e gasométrica no início e fim do MII. Resultados: Foram avaliados 27 e 24 pacientes com e sem FRR, respectivamente. Pacientes sem FRR apresentaram maior aumento de potássio sérico durante o MII (2,67 x 1,14 mEq/L, p < 0,001) atingindo valores mais elevados no fim (6,8 x 5,72 mEq/L, p < 0,001); menor valor de pH no início do intervalo (7,40 x 7,43, p = 0,018), maior proporção de pacientes com bicarbonato sérico < 18 mEq/L (50 x 14,8 %, p = 0,007) e distúrbio ácido-básico misto (70,8 x 42,3 %, p = 0,042), além de maior ganho de peso interdialítico (14,67 x 8,87 mL/kg/h, p < 0,001) e menor natremia (137 x 139 mEq/L, p = 0,02) no fim do intervalo. A calcemia e fosfatemia não foram diferentes entre os grupos. Conclusão: Pacientes com FRR apresentaram melhor controle dos níveis séricos de potássio, sódio, status ácido-básico e da volemia ao longo do MII.

Ocratoxinas y su potencial nefrótico / Ocratoxins and their nephrotoxic potential

Las ocratoxinas son metabolitos fúngicos que están presentes en una gran variedad de alimentos y sus subproductos. La nefrotoxicidad es su principal efecto tóxico, relacionado a su vez con distintos síndromes clínicos como la necrosis tubular o la nefropatía de los Balcanes. La mayor parte de la información que se conoce sobre estas sustancias proviene de reportes de casos, ensayos en animales o estudios experimentales in vitro. Este documento ofrece una visión general sobre las ocratoxinas, su mecanismo tóxico, su efecto nefrotóxico; así como un panorama sobre su regulación actual en Colombia.

Ochratoxins are fungal metabolites that are present in a wide variety of foods and their byproducts. Nephrotoxicity is its main toxic effect, related in turn to different clinical syndromes such as tubular necrosis or Balkan nephropathy. The information that is known about these substances comes from case reports, animal trials or in vitro experimental studies. This document offers an overview of ochratoxins, toxic mechanism, nephrotoxic effect, and a panorama of their current regulation in Colombia.

The effects of local ischemic preconditioning and topical hypothermia in renal ischemia/reperfusion injury in rats

Abstract Purpose: Topical hypothermia and local ischemic preconditioning have been shown to reduce renal ischemia-reperfusion (I/R) injury individually. We examined whether combination of both strategies lessens renal I/R injury. Methods: Post right nephrectomy, 40 male Wistar rats were randomly assigned to five experimental protocols performed in the left kidney: topical hypothermia without ischemia (TH), warm ischemia (IR), ischemic preconditioning followed by warm ischemia (IPC+IR), cold ischemia (TH+IR), and ischemic preconditioning followed by cold ischemia (IPC+TH+IR). Eight randomly assigned right kidneys constituted the control group. After 240 min of reperfusion, the left kidney was retrieved to evaluate histological changes, lipid peroxidation and antioxidant enzymes activity. Serum was collected to evaluate urea and creatinine. Results: IPC+TH+IR group revealed no difference to any other group subjected to ischemia in relation to histological changes, lipid peroxidation and antioxidant enzymes activity. Creatinine was lower in IPC+TH+IR group compared with IPC+IR, but showed no difference compared to TH+IR group. Conclusions: Combination of local ischemic preconditioning (IPC) and topical hypothermia conferred no protection in renal I/R injury. Moreover, local IPC solely followed by warm ischemia impaired renal function more than warm ischemia alone.

Parâmetros hematológicos e perfil bioquímico renal de cordeiros nascidos a termo e prematuros / Hematologic parameters and renal biochemical profile in full-term and premature lambs

O objetivo do presente estudo foi avaliar as variáveis hematológicas e o perfil bioquímico renal sérico de cordeiros nascidos a termo e prematuros do nascimento às 48 horas de vida, bem como verificar a influência da dexametasona sobre tais variáveis. Foram constituídos quatros grupos experimentais: PN (cordeiros nascidos de parto normal, n=15, média de 146 dias); PNDEX (cordeiros nascidos de parto normal cujas mães receberam 16mg de dexametasona aos 141 de gestação, n=8, média de 143 dias); PRE (cordeiros prematuros nascidos de cesarianas aos 138 dias de gestação, n=10) e PREDEX (cordeiros prematuros nascidos de cesarianas aos 138 dias de gestação cujas mães receberam 16mg de dexametasona dois dias antes, n=9). Os valores médios do volume globular e de hemoglobina diminuíram ao longo das 48 horas de observação, nos quatro grupos experimentais, porém dentro dos limites fisiológicos para a espécie. Houve variação da concentração plasmática de proteínas totais em todos os momentos, sendo os menores valores no grupo PRE. A contagem leucocitária foi mais alta no grupo PN apenas no M24h. Ao longo do período, apenas o grupo PN mostrou diferença entre o M24h e os demais momentos, e o grupo PRE apresentou os menores valores de neutrófilos no M0h, M15min e M60min. As concentrações séricas de creatinina foram mais altas no grupo PRE no M60min, M24h e M48h. Em todos os grupos, houve diminuição no M24h e M48h. Os parâmetros avaliados foram afetados pela prematuridade na espécie ovina e a dexametasona teve influência positiva sobre a taxa de sobrevivência dos animais prematuros.(AU)

The aim of the study was to evaluate hematologic parameters and renal biochemical profile of full-term and premature lambs from birth to 48 hours of life, and assess the effect of dexamethasone on such variables. Four experimental groups were formed: NDG (normal delivery group - lambs vaginally delivered, n=15, average of 146-day gestation); NDEXG (normal delivery with dexamethasone group - lambs vaginally delivered whose mothers received 16 mg of dexamethasone at 141 days of gestation, n=8, average of 143-day gestation); PRE (premature lambs born by cesarean section at 138 days of gestation, n=10) and PREDEX (premature lambs born by cesarean section at 138 days gestation, whose mothers received 16 mg of dexamethasone two days before, n=9). Mean values of cell volume and hemoglobin content decreased during the observation period of 48 hours in all groups, but within the physiologic limits for ovine species. There was significant variation in plasma concentration of total protein in all periods evaluated, with the lowest mean values in PRE group. The leukocyte count was significantly higher in PN group only in M24h. Throughout the observation period, only PN group showed differences between M24h and the other moments and PRE group showed the lowest values of neutrophils in M0h, M15min and M60min. Serum creatinine concentration was significantly higher in group PRE in M60min, M24h and M48h. In all groups, there was a decrease in M24 and M48. The evaluated parameters were affected by prematurity in sheep and dexamethasone had a positive effect on the survival rate of premature animals.(AU)

Effects of hypertonic saline solution associated to remote ischemic perconditioning in kidney ischemia/reperfusion injury in rats

Abstract Purpose: To evaluate the effects of hypertonic saline solution associated to remote ischemic perconditioning in renal ischemia/reperfusion injury in rats. Methods: Twenty five male rats (Wistar) underwent right nephrectomy and were distributed into five groups: Sham group (S); Ischemia/Reperfusion group (I/R) with 30 minutes of renal ischemia; Remote ischemic perconditioning group (Per) with three cycles of 10 minutes of I/R performed during kidney ischemia; Hypertonic saline solution group (HSS) treated with hypertonic saline solution (4ml/kg); remote ischemic perconditioning + Hypertonic saline solution group (Per+HSS) with both treatments. After reperfusion, blood samples were collected for BUN and creatinine serum levels analyzes. TBARS were evaluated in plasma and renal tissue to assess oxidative stress. Kidney histopathological examination were performed. Results: Per+HSS group showed a lower degree of renal dysfunction in relation to I/R group, whereas the technique of remote ischemic perconditioning isolated or associated with saline solution significantly reduced oxidative stress and histological damage. Conclusion: Remote ischemic perconditioning associated or not to saline solution promoted reduction of acute renal injury induced by ischemia/reperfusion.

Dexmedetomidine preconditioning inhibits the long term inflammation induced by renal ischemia/reperfusion injury in rats

PURPOSE: To investigate the protective effects of dexmedetomidine (Dex) against renal ischemia/reperfusion injury (IRI). METHODS: Sprague-Dawley rats were randomly divided to sham group, IRI group and Dex group. The SD rats were subjected to 45 min of ischemia followed by eight weeks of reperfusion. Prior to ischemia, rats were either treated with Dex or not. Blood samples were collected for the detection of blood urea nitrogen (BUN) and creatinine (Cr) levels. Immunohistochemistry was performed for CD3 T-cell infiltrates. Real-time PCR and western blot were detected for the expression of TNF-α, IL-1β, ICAM-1, HMGB1 and TLR4. RESULTS: Compared with sham group, renal IRI significantly increased the serum levels of BUN and Cr. The H&E staining indicated that renal IRI resulted in obvious renal injury and immunohistochemistry found that there were more CD3 T-cell infiltrates in IRI group. Also, renal IRI upregulated the expression of TNF-α, IL-1β, ICAM-1, HMGB1 and TLR4. However, all these changes were alleviated by the treatment with Dex. CONCLUSIONS: Dexmedetomidine has beneficial effects on long term inflammation induced by renal ischemia/reperfusion injury. Its mechanisms may be achieved through inhibiting the HMGB1/TLR4 pathway to exert protective effects.

Concentrations of strontium, barium, cadmium, copper, zinc, manganese, chromium, antimony, selenium, and lead in the liver and kidneys of dogs according to age, gender, and the occurrence of chronic kidney disease

This study was conducted to measure the concentrations of strontium (Sr), barium (Ba), cadmium (Cd), copper (Cu), zinc (Zn), manganese (Mn), chromium (Cr), antimony (Sb), selenium (Se), and lead (Pb) in canine liver, renal cortex, and renal medulla, and the association of these concentrations with age, gender, and occurrence of chronic kidney disease (CKD). Tissues from 50 dogs were analyzed using inductively coupled plasma mass spectrometry. Cu, Zn, and Mn levels were highest in the liver followed by the renal cortex and renal medulla. The highest Sr, Cd, and Se concentrations were measured in the renal cortex while lower levels were found in the renal medulla and liver. Female dogs had higher tissue concentrations of Sr (liver and renal medulla), Cd (liver), Zn (liver and renal cortex), Cr (liver, renal cortex, and renal medulla), and Pb (liver) than male animals. Except for Mn and Sb, age-dependent variations were observed for all element concentrations in the canine tissues. Hepatic Cd and Cr concentrations were higher in dogs with CKD. In conclusion, the present results provide new knowledge about the storage of specific elements in canine liver and kidneys, and can be considered important reference data for diagnostic methods and further investigations.

Renal Klotho expression in patients with acute kidney injury is associated with the severity of the injury

BACKGROUND/AIMS: The potential physiologic roles of Klotho in acute kidney injury (AKI) have recently been demonstrated in animal models. However, to date, there have been no human studies investigating the expression of renal Klotho in AKI. METHODS: We retrospectively collected biopsy specimens and clinical data of AKI patients between January 2001 and December 2012. Klotho expression was determined by immunohistochemical staining, and the clinical-pathological correlation was examined. RESULTS: Among the 34 patients diagnosed with acute tubular necrosis or acute tubulointerstitial nephritis, 21 patients without chronic histological lesions were included. The mean age was 37.3 +/- 18.5 years and the mean peak creatinine level was 8.2 +/- 5.5 mg/dL. In total, 10 patients (47.6%) received temporary renal replacement therapy (RRT); however, 17 patients (81%) showed functional recovery with creatinine levels of < 1.3 mg/dL after 1 month. The intensity of Klotho expression was scored as a percentage of Klotho-positive area. The renal Klotho score showed a significant negative correlation with the initial or peak creatinine level. When the patients were divided into three groups according to the Klotho score (low, middle, high), the low group had a significantly higher peak creatinine level and a more frequent requirement for RRT. However, the Klotho score was not a significant predictor of renal recovery. CONCLUSIONS: The results demonstrated that renal Klotho expression in humans decreased significantly according to the severity of AKI, regardless of the etiology, and that low expression was associated with a poor short-term outcome.

Role of Mesenchymal Stem Cell Therapy in Cisplatin Induced Nephrotoxicity in Adult Albino Rats: Ultrastructural & Biochemical Study.

Objective: Mesenchymal stem cells (MSCs) have generated a great deal of excitement and promise as a potential source of cells for cell-based therapeutic strategies. These data provide the clue of using MSCs in the current work in correcting cisplatin-induced nephrotoxicity, the severest adverse effect of the well-known anticancer drug; cisplatin. Methods: MSCs of bone marrow origin of femora and tibiae of adult albino rats were separated, grown, propagated in culture then identified by both morphology and CD29 surface marker detection. MSCs were injected into the rats’’ tail veins one day after a single dose (5 mg/kg body weight) of intraperitoneal injection of cisplatin. Four weeks later kidney tissue was examined histopathologically and ultra-structurally. Renal functions s(urea, creatinine) as well as serum electrolytes levels (Na, K) were estimated Results: Cisplatin group demonstrated atrophied glomeruli, thickened glomerular basement membrane, dilated urinary space, loss of proximal convoluted tubules brush borders, loss of podocyte pedicels and collagen deposition. Tubular cells showed vacuolization and nuclear membrane degeneration. Serum levels of urea, creatinine, Na and K were significantly elevated. MSCs ameliorated cisplatin-induced nephrotoxicity to a great extent as evidenced histologically, ultra-structurally and biochemically. Conclusion: MSCs have a potential therapeutic effect against cisplatin induced nephrotoxicity.

Effect of castration on renal glycosaminoglycans and their urinary excretion in male and female rats with chronic renal failure

Glycosaminoglycans (GAGs) participate in a variety of processes in the kidney, and evidence suggests that gender-related hormones participate in renal function. The aim of this study was to analyze the relationship of GAGs, gender, and proteinuria in male and female rats with chronic renal failure (CRF). GAGs were analyzed in total kidney tissue and 24-h urine of castrated (c), male (M), and female (F) Wistar control (C) rats (CM, CMc, CF, CFc) and after 30 days of CRF induced by 5/6 nephrectomy (CRFM, CRFMc, CRFF, CRFFc). Total GAG quantification and composition were determined using agarose and polyacrylamide gel electrophoresis, respectively. Renal GAGs were higher in CF compared to CM. CRFM presented an increase in renal GAGs, heparan sulfate (HS), and proteinuria, while castration reduced these parameters. However, CRFF and CRFFc groups showed a decrease in renal GAGs concomitant with an increase in proteinuria. Our results suggest that, in CRFM, sex hormones quantitatively alter GAGs, mainly HS, and possibly the glomerular filtration barrier, leading to proteinuria. The lack of this response in CRFMc, where HS did not increase, corroborates this theory. This pattern was not observed in females. Further studies of CRF are needed to clarify gender-dependent differences in HS synthesis.

Differencial proteome of clear-cell renal cell carcinoma (ccRCC) tissues

Purpose We attempted to detect, for the first time in a Brazilian cohort, differences in protein expression between clear-cell renal cell carcinoma (ccRCC) and their normal adjacent tissues, aiming to identify biomarkers and/or therapeutic target candidates for this disease. Material and Methods Twenty-four ccRCC and adjacent normal tissues were collected after surgery and their protein extracts were quantified, pooled and separated by two-dimensional polyacrylamide gel electrophoresis (2DE), followed by statistical analysis of the stained gels. Spots of interest were excised from the gels, digested with trypsin and identified by MALDI-TOF-TOF mass spectrometry. Results Twenty-six differential spots were detected between the two classes of tissues, among which twenty were identified by mass spectrometry and sixteen were found to be non-redundant. Eleven proteins were either underexpressed or undetected in the ccRCC extracts, such as prohibitin and peroxiredoxin-3, whereas five were found to be overexpressed or exclusively detected in the ccRCC extract, including αβ crystalin and heat shock protein 27. CONCLUSIONS Several proteins were detected at differential levels when compared to normal adjacent tissues, and, moreover, many have been previously described by their relationship with RCC. Therefore, this work corroborates previous reports on the search for biomarkers for ccRCC, as well as it points out new candidates that may be validated in future studies. .

The impact of gender, age and tissues in vitro on estimating postmortem interval by FTIR spectroscopy / 法医学杂志

To investigate the influence of such individual factors as gender, age and tissues in vitro to the postmortem interval (PMI) by the Fourier transform infrared (FTIR) spectrometer in animal experiments. SD rats were classified into male and female groups, different age groups (21-day, 42-day and 63-day group), and tissues in vitro and in vivo groups. The rats were sacrificed by cervical dislocation, whose bodies were kept in a controlled environmental chamber set at (20+/-2) degrees C and 50% humidity. The liver, kidney, spleen, myocardium, brain, lung and skeletal muscle tissues were collected for measurement from time zero to 48 h postmortem. With the change of PMI, no obvious changes were found in the main FTIR absorbance peaks and their ratios at different time points. All the experimental groups showed no significant changes when compared with the controls. The gender, age and tissues in vitro were not found to be contributing factors in the estimation of PMI via FTIR spectroscopy.

Localization of sulphonylurea receptor proteins SUR2A and SUR2B and/or SUR1 in rat kidney

To further explore precise expression and localization of sulphonylurea receptor isoforms SUR2A and SUR2B [SUR1] in rat kidney, total RNA was isolated from the kidney tissue using the TRIzol kit. Three different primer sets designed against SUR isoforms were used in reverse transcriptase reactions. Western blotting was done on membrane fractions obtained from kidney tissues using the primary antisera for SUR2A and SUR2B [SUR1]. Paraformaldehyde fixed kidney sections were immunostained with SUR2A and SUR2B [SUR1] primary antisera. Sections were developed with DAB as a chromogen. RT-PCR results demonstrated mRNA consistent with SUR1 isoform to be the only identifiable transcript. Western blotting could not identify any protein consistent with SUR2A or SUR2B [SUR1] but recognized instead a smaller 55kD protein of unknown identity. Immunohistochemistry demonstrated a differential staining pattern whereby SUR2A was localized to the mesangial cells, intra- and extrarenal blood vessels and smooth muscles. In contrast, SUR2B [SUR1] was localized only to distal nephron epithelia. Intense immunoreactivity was localized to the thick ascending limb and as well as in the outer and inner medullary collecting ducts, both. Our results demonstrate differential and highly localized expression pattern of sulphonylurea receptor proteins SUR2A and 2B [SUR1] in rat kidney with implications for drug design

Postmortem distribution of tetrodotoxin in tissues and body fluids of guinea pigs / 法医学杂志

OBJECTIVE@#To investigate the postmortem distribution of tetrodotoxin in tissues and body fluids of guinea pig, and to provide method and evidence for forensic identification and clinical diagnosis and treatment.@*METHODS@#Guinea pigs were intragastric administrated with 100, 50, 15 microg/kg tetrodotoxin, respectively. The poisoning symptoms were observed. The samples of heart, liver, spleen, lung, kidney, brain, stomach, intestines, bile, heart blood and urine were collected. The concentrations of tetrodotoxin in tissues and body fluids were measured with liquid chromatography-tandem mass spectrometry (LC-MS/MS).@*RESULTS@#After administrated with tetrodotoxin, all guinea pigs came out poisoning signs including tachypnea, weary and dead finally. Tetrodotoxin concentrations in lung, stomach, intestines and urine were higher, followed by blood, heart and brain. The concentration in bile was the lowest.@*CONCLUSION@#Postmortem distribution of tetrodotoxin in guinea pig is uneven. The concentration in the lung, stomach, intestines, urine and heart blood are higher, those tissues could be used for diagnosis of tetrodotoxin poisoning.

Manifestaciones clínicas y cambios en la química sérica y tisular en ratas tratadas con vitamina D3 (calciferol) / Clinical signs and changes in serum and tissue chemistry in rats treated with vitamin D3 (calciferol)

En el presente trabajo se estudió el efecto de la administración subcutánea de 250, 500 y 750 μg (10.000, 20.000 y 30.000 UI, respectivamente) de vitamina D3 (calciferol)/día durante 8 días, sobre las concentraciones séricas de vitamina D3 y de 25-hidroxivitamina D3 (25-OH-D3) y sobre las concentraciones séricas y tisulares de Ca, Zn, Cu y Fe en 45 ratas macho Wistar, de 12 semanas de edad y con pesos entre 180 y 200 gramos. El grupo control estuvo integrado por 15 ratas Wistar sanas, con género, edad y peso similares a los animales tratados. La administración del calciferol a dosis altas produjo una hipervitaminosis D que se caracterizo por un aumento en el contenido sérico de la vitamina D3 y de 25-OH-D3, diversos signos clínicos (por ejemplo, anorexia, pérdida marcada de peso, diarreas sanguinolentas, conjuntivitis bilateral y muerte), hipercalcemia, hipocincemia, hipercupremia, hipoferremia y una alteración en la distribución tisular de Ca, Zn, Cu y Fe en comparación con los controles no tratados. La hipercalcemia y la inflamación son un hallazgo prominente en la hipervitaminosis D. La inflamación o la infección inducen cambios sistémicos, conocidos colectivamente como la respuesta de fase aguda. Entre las variadas alteraciones que produce esta respuesta encontramos hipoferremia, hipocincemia e hipercupremia. Es probable que estas respuestas estén mediadas, en parte, por la producción y liberación de citocinas como la interleucina 1, interferones (IFN-alfa), la interleucina 6 (Il-6) y el factor de necrosis tumoral (TNF). El desarrollo de la hipoferremia durante la inflamación requiere de hepcidina, un péptido rico en enlaces disulfuro, regulador del metabolismo del hierro, sintetizado en el hígado en respuesta a la liberación de Il-6 durante la inflamación/infección. En conclusión, nuestros resultados proporcionan evidencias que la administración de altas dosis de vitamina D, a corto plazo, determina diversos signos clínicos, produce un marcado aumento de las concentraciones séricas de la vitamina D3 y de 25-OH-D3 y una marcada alteración en las concentraciones séricas y tisulares de Ca, Zn, Cu y Fe, que dependen de las dosis inyectadas de vitamina D.

In the present work the effect of subcutaneous administration of 250, 500 and 750 ìg (10.000, 20.000 and 30.000 IU, respectively) of vitamin D3 (calciferol) daily for eight days, on serum concentrations of vitamin D3 and 25- hydroxyvitamin D3 (25-OH-D3) and on serum and tissue concentrations of Ca, Zn, Cu and Fe in 45 white male Wistar rats, aged 12 weeks and weighing 180-200 g, have been studied. The group control was integrated by 15 healthy rats with similar characteristics (strain, gender, age and weight) that treated animals. Administration of high doses of calciferol produced a hypervitaminosis D characterized by a significant (p3 and 25-OH-D3, diverse clinical signs (such as, anorexia, marked loss of body weight, bloody diarrhea, bilateral conjunctivitis, and death), hypercalcemia, hypozincaemia, hypercupremia, hypoferraemia and an alteration in the tissue distribution of Ca, Zn, Cu and Fe as compared with untreated controls. Hypercalcemia and inflammation are prominent findings in hypervitaminosis D. Inflammation or infection induce systemic changes, collectively known as the acute phase response. Among the varied alterations that together produce this response are hypoferraemia, hypozincaemia and hypercupremia. It is likely that these responses are mediated, in part, by production and release of cytokines such as interleukin 1, interferons (IFN-alpha), interleukin 6 (Il-6) and tumor necrosis factor (TNF). The development of hypoferraemia during inflammation requires hepcidin, an iron regulatory hormone, a disulfide-rich peptide, produced in the liver in response to the release of Il-6 during inflammation/ infection. In conclusion, our results provide evidence that short-term administration of high doses of vitamin D determined diverse clinical signs and produced a marked increase of serum vitamin D3 and 25-OH-D3 and a marked alteration in the serum and tissue concentrations of Ca, Zn, Cu, and Fe. These changes depend on the doses given of vitamin D.

Stability of estazolam in dog tissues preserved in formaldehyde solution / 法医学杂志

OBJECTIVE@#To investigate the stability of estazolam in biological samples preserved in formaldehyde solution.@*METHODS@#The dog was given intragastric administration of estazolam with a dose of 37.6 mg/kg and killed 2 h later. Heart, liver, kidney and brain of the dog were cut up into 1 g and preserved in 4% formaldehyde solution respectively. The content of estazolam in biological samples and formaldehyde solution were analyzed by HPLC at different times.@*RESULTS@#The content of estazolam in heart, liver, kidney and brain or in formaldehyde solution reduced gradually followed with the extention of preservation time. At the 63rd day, estazolam content in four tissues were 0.8%, 1.7%, 1.0% and 2.2% of the original content respectively.@*CONCLUSION@#Estazolam in tissues can diffuse into formaldehyde solution and decomposed quickly, so biological samples contained estazolam should not be preserved in formaldehyde solution.

Low dose gamma irradiation modifies the effect of L-carnitine, curcumin, garlic powder and green tea extract on doxorubicin-induced nephropathy in rats

The possible protective potential of exposure to low dose of gamma radiation in presence or absence of L-carnitine, curcumin, garlic powder or green tea extract was examined in the present study on doxorubicin [DOX]-induced experimental nephropathy in rats. Preliminary study was carried out to select the suitable dose of DOX to induce nephrotoxicity. In the current experiment 5 mg/kg, i.p. was selected as a single dose to induce nephrotoxicity during 15 days. The possible modulating effect of L-carnitine, curcumin, garlic powder or green tea extract on kidney function was examined. Animals were subdivided into three sets. Three groups of the 1[st] set were exposed to [gamma] radiation at a single dose level of 0.3 Gy then received DOX, 1, 3 or 7 days postirradiation respectively. The groups of 2[nd] set daily received L-carnitine [40 mg/kg, i.p.], curcumin [50 mg/kg, i.p.], garlic powder [100 mg/kg, p.o.] and green tea extract [300 mg/kg, p.o.] daily for two weeks before induction of nephropathy. Groups of the 3[rd] set received the same doses of drugs then were injected with DOX, 1, 3 or 7 days following gamma irradiation respectively. Two groups of animals, one of them received saline and served as normal and the other received DOX and served as nephropathic group were included in 1[st], 2[nd] as well as 3[rd] set. Fifteen days following DOX administration, serum was collected and the animals were then sacrificed. Serum creatinine, urea and uric acid were evaluated. Data revealed that, a single DOX dose [5 mg/kg] induced marked acute nephrotoxicity manifested as significant increase in the activities of serum creatinine, urea as well as uric acid. Interestingly, pre-exposure to gamma radiation at a dose level of 0.3 Gy, 1 or 3 days before DOX injection exhibited significant improvement in the above altered mentioned parameters. However, exposure to low dose radiation 7 days prior to DOX administration did not show a protective effect. Moreover, pretreatment with L-carnitine, curcumin, garlic powder or green tea extract in rats unexposed or exposed to gamma radiation before DOX administration ameliorated, to a great extent, the effects induced by DOX. The present findings suggest that exposure to a single low dose of gamma radiation [0.3 Gy] one day before DOX administration is a promising approach for maximizing the nephroprotective effects of L-carnitine, curcumin, garlic powder or green tea extract with minimal adverse effects of DOX

Primary hyperoxaluria type 1 with a novel mutation.

Primary hyperoxaluria type 1 [PH1] is an autosomal recessive disorder caused by a deficiency of alanine-glyoxylate aminotransferase AGT, which is encoded by the AGXT gene. We report an Indian family with two affected siblings having a novel mutation in the AGXT gene inherited from the parents. The index case progressed to end stage renal disease at 5 months of age. His 4 month old sibling is presently under follow up with preserved renal function.

Study on correlations among ceruloplasmin, copper of serum, liver and kidney of goats in shahrekord slaughterhouse

In order to determine the copper status and correlation between the ceruloplasmin and copper of serum and among the copper of serum, liver and kidney of slaughtered goats in Shahrekord, blood, liver and kidney samples [10 gr] from 100 goats were gathered. The amounts of ceruloplasmin and copper of serum, liver and kidney were measured by Sunderman - Nomoto and Shimadzu atomic absorption method, respectively. Results were analyzed by Pearson correlation test, Chi square test. The mean serum ceruloplasmin value of goats was 190_40.2 mg/L. The corresponding value for the copper of serum was 14.32 +/- 2.42 micro mol/L. Mean liver and kidney copper levels were respectively 4596.08 +/- 1967.5 and 271.98 +/- 59.81 micro mol/Kg. There was a significant correlation [p < 0.05] between the level of ceruloplasmin and copper of serum [r = 0.85]. There was also a correlation [p < 0.05] between copper of serum and liver [r = 0.56], copper of serum and kidney [r = 0.36] and copper of liver and kidney [r = 0.22]. Kidney copper concentration in 7% of goats were lower than 199.89 micro mol/Kg and serum copper level in 4% of goats were between 6.29-11.01 micro mol/L. They indicated that between 4 to 7 percent of goats had marginal copper deficiency. Data shows low correlation among variables and only correlation between serum copper and ceruloplasmin was high. It could be concluded that copper deficiency can occur under certain conditions in Shahrekord

Effects of paraquat on anti-oxidant system in rats.

The toxic effects of paraquat on the anti-oxidant defense system of male albino rats were evaluated, after administering either a single dose (1.5 and 7.5 mg/kg of body weight) or continuous daily doses (same as above, i.e., 1.5 mg/kg and 7.5 mg/kg of body weight) for 3 and 7 days. Glutathione levels in blood cells, liver, lung and kidney tissues decreased in a dose and time dependent manner. Glutathione reductase and glucose-6-phosphate dehydrogenase activity decreased, whereas the activity of glutathione-S-transferase, glutathione peroxidase, catalase and superoxide dismutase increased in paraquat exposure. Malondialdehyde formation also increased in a dose and time dependent manner. The alterations of anti-oxidant system particularly glutathione can be utilized as biomarkers during management of paraquat poisoning.