Prolonged Administration of Rudgea viburnoides (Cham.) Benth. Prevents Impairment of Redox Status, Renal Dysfunction, and Cardiovascular Damage in 2K1C-Hypertensive Rats by Inhibiting ACE Activity and NO-GMPC Pathway Activation.

Rudgea viburnoides is widely found in the Brazilian Cerrado, and commonly used in Brazilian folk medicine. In this study, we evaluated the effects of prolonged administration of the aqueous extract from R. viburnoides leaves (AERV) on impaired redox status, renal dysfunction, and cardiovascular damage in 2K1C hypertensive rats, as well as its chemical composition by LC-DAD-MS. Renal hypertension (two kidney, one-clip model) was surgically induced in male Wistar rats and AERV (30, 100 and 300 mg/kg) was administered orally five weeks after surgery for 28 days. Renal function was assessed and urinary electrolytes, pH, and density were measured. Electrocardiography, blood pressure and heart rate were recorded. Cardiac and mesenteric vascular beds were isolated for cardiac morphometry and evaluation of vascular reactivity, and aortic rings were also isolated for measurement of cyclic guanosine monophosphate levels, and the redox status was assessed. Prolonged treatment with AERV preserved urine excretion and electrolyte levels (Na+, K+, Ca2+ and Cl-), reversed electrocardiographic changes, left ventricular hypertrophy and changes in vascular reactivity induced by hypertension, and reduced blood pressure and heart rate. This effect was associated with a positive modulation of tissue redox state, activation of the NO/cGMP pathway, and inhibition of the angiotensin-converting enzyme. Glycosylated iridoids, chlorogenic acids, glycosylated triterpenes, O-glycosylated flavonols, and triterpenoid saponins were annotated. AERV showed no acute toxicity in female Wistar rats. Therefore, AERV treatment reduced the progression of cardiorenal disease in 2K1C hypertensive rats, which can be involved with an important attenuation of oxidative stress, angiotensin-converting enzyme inhibition, and activation of the NO/cGMP pathway.

Cardioprotective effects of Talinum paniculatum (Jacq.) Gaertn. in doxorubicin-induced cardiotoxicity in hypertensive rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Talinum paniculatum (Jacq.) Gaertn. (Talinaceae) is a medicinal species that is widely distributed throughout Brazil. Popularly known as "major-gomes," the species is used in folk medicine for the treatment of cardiovascular disorders. AIM OF THE STUDY: To evaluate the effect of an ethanolic extract of T. paniculatum (EETP) in rats with renovascular hypertension and heart failure and determine its chemical composition. MATERIALS AND METHODS: First, EETP was obtained, and its chemical profile was analyzed by LC-DAD-MS. The acute toxicity was evaluated in female Wistar rats. The model of renovascular hypertension was established in male Wistar rats by combining the Goldblatt 2K1C method and intraperitoneal doxorubicin administration for 6 weeks. The animals were then treated daily with EETP (30, 100, and 300 mg/kg) or metoprolol (25 mg/kg) by gavage for 28 days. The negative control group was treated with vehicle (filtered water). The sham group consisted of animals that were not subjected to 2K1C or cardiotoxicity and were treated with vehicle. Renal function was evaluated on days 1, 14, and 28. At the end of treatment, the electrocardiographic profile, blood pressure, and mesenteric vascular reactivity were investigated. Serum urea, creatinine, angiotensin converting enzyme, nitrotyrosine, malondialdehyde, nitrite, aldosterone, and sodium and potassium levels were measured. The heart, aorta artery, liver, and right kidney were collected, weighed, and processed for histopathological analysis. Cardiac chambers also underwent morphometric analysis. RESULTS: No signs of toxicity were observed in female Wistar rats. Thirty-two compounds were annotated from EETP, including flavonoids, chlorogenic acids, and saponins. EETP treatment resulted in a significant cardiorenal-protective response, normalizing electrocardiographic and hemodynamic alterations, and preventing ventricle remodeling. These effects were associated with serum antioxidant activity and angiotensin-converting enzyme (ACE) inhibition. CONCLUSION: The present study demonstrated that EETP may exert cardioprotective effects through serum antioxidant activity and ACE inhibition, preventing alterations of hemodynamic and endothelial function, and reducing damage to cardiac structure. Thus, EETP, especially at the 100 and 300 mg/kg doses, may be useful for preventing doxorubicin-induced cardiotoxicity in hypertensive patients.

Atheroprotective Properties of Costus spicatus (Jacq.) Sw. in Female Rats.

BACKGROUND: Costus spicatus (Jacq.) Sw. is a medicinal species frequently prescribed for the treatment of cardiovascular diseases. This study aims to evaluate the effects of this species against the development of atherosclerosis. METHODS: First, an anatomical study of the C. spicatus leaves was performed. Then, the extract (ESCS) was obtained and submitted to phytochemical analysis. Female rats were treated with a single dose of ESCS (2000 mg/kg) to assess acute toxicity. Other groups of female rats received an atherogenic diet for 60 days. After 30 days, the animals were treated orally with ESCS (30 and 300 mg/kg), rosuvastatin (5 mg/kg), or vehicle once daily for 30 days. Serum lipids oxidized low-density lipoprotein, soluble adhesion molecules, interleukins 1ß and 6, and markers of renal and liver function were measured. Renal function, blood pressure, electrocardiography, and vascular reactivity were also evaluated. Arteries, heart, liver, and kidney were also collected to evaluate the tissue redox state and histopathological analysis. RESULTS: Prolonged treatment with ESCS induces significant hypolipidemic and antioxidant effects, that prevent endothelial dysfunction and modulated the local inflammatory process, reducing the evolution of the atherosclerotic disease. CONCLUSIONS: This study provides a scientific basis for the popular use of C. spicatus for the treatment of atherosclerosis.

Ethnopharmacological investigation of the cardiovascular effects of the ethanol-soluble fraction of Aloysia polystachya (Griseb.) Moldenke leaves in spontaneously hypertensive rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Aloysia polystachya (Griseb) Moldenke (Verbenaceae), popularly known as "burrito", is a South American species widely prescribed by local Brazilian healers for the treatment of cardiovascular diseases. However, its antihypertensive and cardioprotective effects are still unknown. AIM: To evaluate the role of the ethanol-soluble fraction of A. polystachya leaves (ESAP) against hypertension in spontaneously hypertensive rats (SHRs), as well as its safety, morphoanatomical and phytochemical aspects. MATERIALS AND METHODS: First, the leaves and stems of A. polystachya were analyzed by optical and scanning electron microscopy in order to provide anatomical data for quality control. Then, ESAP was obtained and its chemical profile was analyzed by LC-DAD-MS. In addition, the cytotoxic and acute toxicity potential of ESAP were evaluated in six cell lines and in female Wistar rats, respectively. Next, female spontaneously hypertensive rats (SHRs) received ESAP (30, 100, 300 mg/kg), hydrochlorothiazide (25 mg/kg), or vehicle once daily for 28 days. Weekly kidney function was monitored by analyzing urinary parameters. At the end of the 28-day treatment, the electrocardiographic profile, blood pressure, and renal and mesenteric vascular reactivity were evaluated. Relative organ (heart, kidney, and liver) weights and biochemical parameters were also evaluated. Finally, the heart, kidneys, and aorta were collected for determination of the tissue redox state, cardiac morphometry, and histopathological analysis. RESULTS: The chemical profile of ESAP was composed by organic acids, a nucleoside, methoxylated flavones and glycosylated compounds including phenolic acids, phenylpropanoids, iridoids and monoterpenes. No signs of toxicity were observed in all cell's lines nor in female Wistar rats submitted to this trial. All SHRs from the negative control group presented a reduction in renal function, alterations in the renal and mesenteric vascular reactivity, and electrocardiographic and morphometric changes typical of ventricular hypertrophy. Oral prolonged ESAP-administration in SHRs was able to reverse renal, electrocardiographic and hemodynamic changes induced by hypertension. Moreover, ESAP-treatment was able to modulate the vascular and renal arterial reactivity and tissue redox state. The aforementioned data were accompanied by reduction of cardiac hypertrophy. CONCLUSION: In this study, we present important anatomical and phytochemical data that contributed to the correct identification and quality control of A. polystachya. In addition, we have shown that ESAP is safe after acute administration and present significant cardioprotective effects (at 30, 100, and 300 mg/kg doses) in SHRs after prolonged treatment.

Ethnopharmacological investigations of the leaves of Cecropia pachystachya Trécul (Urticaceae): A native Brazilian tree species.

ETHNOPHARMACOLOGICAL RELEVANCE: Cecropia pachystachya Trécul (Urticaceae) is a medicinal plant popularly known as 'embaúba'. In Brazil, the leaves of this species are used for the treatment of various kidney and cardiovascular diseases. However, there are no detailed studies on the renal and cardiovascular activities of this species. No studies on the anatomy or the quality control of this herbal drug is available thus far. AIM: This study was aimed to investigate the ethnopharmacological properties of the leaves of C. pachystachya. MATERIAL AND METHODS: The leaves of C. pachystachya were analyzed by light and scanning electron microscopy for pharmacobotanical and anatomical characterization. The ethanol-soluble fraction of C. pachystachya leaf extract (ESCP) was characterized by high-performance liquid chromatograph equipped with diode array detector and mass spectrometry (HPLC-DAD-MS). The acute oral toxicity of ESCP on female Wistar rats was assessed. The acute and prolonged diuresis and antioxidant effects of ESCP (30, 100, and 300 mg/kg) were evaluated in male Wistar rats. In addition, the hypotensive effects of the ESCP as well as the vasodilatory activity in isolated and perfused mesenteric vascular beds were investigated. RESULTS: The anatomical markers obtained in this study can help in the identification of C. pachystachya, as well as to distinguish it from the other 'embaúbas'. The metabolites found in the ESCP were phenolic compounds, mainly C- and O-glycosylated flavonoids. The ESCP did not exhibit any toxic effects at a dose of 2000 mg/kg. Significant diuretic activities were observed at the doses of 30, 100, and 300 mg/kg. In addition, a significant modulating activity of the tissue redox state was observed after prolonged treatment. On the other hand, no hypotensive or vasodilator activity was observed. CONCLUSION: The key findings of the present study can contribute to the taxonomy, species identification and quality control of C. pachystachya. Chemical studies have shown the presence of glycosylated flavonoids, phenylpropanoid derivative and proanthocyanidins. The pharmacological studies showed significant diuretic and antioxidant effects of C. pachystachya leaf extract, indicating a possible validation of its popular medicinal use.

Cuphea calophylla var. mesostemon (Koehne) S.A. Graham: A Whole-Ethnopharmacological Investigation.

Several species of Cuphea are used medicinally and are reported to have cardioprotective, diuretic, and antihypertensive properties. In Brazil, Cuphea species are collectively called "sete-sangrias" due to their similar appearances and are also used interchangeably for the same therapeutic purposes. So the aim of the study was to characterize morphoanatomy of leaves and stems, evaluate the safety, and investigate the diuretic, hypotensive, vasodilatory, and antioxidant properties of ethanol-soluble fraction of Cuphea calophylla var. mesostemon (Koehne) S.A. Graham. Initially, the morphoanatomical characterization of the leaves and stems of C. calophylla var. mesostemon was performed. For the pharmacological evaluation, the ethanol-soluble fraction from Cuphea calophylla (ESCC) was obtained and chemically characterized by high-performance liquid chromatography coupled with a diode array detector and tandem mass spectrometry techniques. Then, acute toxicity, diuretic, hypotensive, antioxidant, and vasodilatory effects were evaluated in Wistar rats. The main chemical compounds identified from ESCC were gallic acid derivatives, ellagitannins, and flavonoids. ESCC showed no acute toxic effect. ESCC showed no acute toxic effect and the estimated median lethal dose (LD50) was above 2000 mg/kg. ESCC treatment (30, 100, and 300 mg/kg) did not present any significant acute diuretic or hypotensive effects. However, an important reduction in the elimination of electrolytes was observed after the acute administration, and a significant increase in renal sodium elimination was observed after 7 days of treatment. In the cardiac tissue, the groups treated with ESCC presented significant increase in superoxide dismutase activity.

Nephroprotective and antilithiatic activities of Costus spicatus (Jacq.) Sw.: Ethnopharmacological investigation of a species from the Dourados region, Mato Grosso do Sul State, Brazil.

ETHNOPHARMACOLOGICAL RELEVANCE: Costus spicatus (Jacq.) Sw., also known as "cana-do-brejo," is a species that is widely used in Brazilian traditional medicine for the treatment of kidney diseases. However, no studies have evaluated its nephroprotective and antilithiatic effects. AIM: To investigate nephroprotective and antilithiatic effects of C. spicatus in a preclinical model of acute kidney injury (AKI) and in vitro nephrolithiasis. MATERIALS AND METHODS: C. spicatus leaves were collected directly from the natural environment in the Dourados region, Mato Grosso do Sul State, Brazil. The ethanol-soluble fraction of C. spicatus (ESCS) was obtained by infusion. Phytochemical characterization was performed by liquid chromatography coupled to diode array detector and mass spectrometer (LC-DAD-MS). We assessed whether ESCS has acute or prolonged diuretic activity. The nephroprotective effects of ESCS were evaluated in a model of AKI that was induced by glycerol (10 ml/kg, intramuscularly) in Wistar rats. Different doses of ESCS (30, 100, and 300 mg/kg) were administered orally for 5 days before the induction of AKI. Urinary parameters were measured on days 1, 3, 5, and 7. Twenty-four hours after the last urine collection, blood samples were obtained for the biochemical analysis. Blood pressure levels, renal vascular reactivity, renal tissue redox status, and histopathological changes were measured. Antilithiatic effects were evaluated by in vitro crystallization. Calcium oxalate precipitation was induced by sodium oxalate in urine samples with ESCS at 0.05, 0.5, and 5 mg/ml. RESULTS: From LC-DAD-MS analyses, flavonoids, saponins and other phenolic compounds were determined in the composition of ESCS. Significant reductions of the excretion of urinary total protein, creatinine, sodium, and potassium were observed in the AKI group, with significant histopathological damage (swelling, vacuolization, necrosis, and inflammatory infiltration) in the proximal convoluted tubule. Treatment with ESCS exerted a significant nephroprotective effect by increasing the urinary excretion of total protein, urea, creatinine, sodium, potassium, calcium, and chloride. All of the groups that were treated with ESCS exhibited a reduction of histopathological lesions and significant modulation of the tissue redox state. We also observed a concentration-dependent effect of ESCS on the crystallization of urinary crystals, with reductions of the size and proportion of monohydrated crystals. CONCLUSION: The data suggest that C. spicatus has nephroprotective and antilithiatic effects, suggesting possible effectiveness in its traditional use.

Preventing Occupational Tuberculosis in Health Workers: An Analysis of State Responsibilities and Worker Rights in Mozambique.

Given the very high incidence of tuberculosis (TB) among health workers in Mozambique, a low-income country in Southern Africa, implementation of measures to protect health workers from occupational TB remains a major challenge. This study explores how Mozambique's legal framework and health system governance facilitate-or hinder-implementation of protective measures in its public (state-provided) healthcare sector. Using a mixed-methods approach, we examined international, constitutional, regulatory, and policy frameworks. We also recorded and analysed the content of a workshop and policy discussion group on the topic to elicit the perspectives of health workers and of officials responsible for implementing workplace TB policies. We found that despite a well-developed legal framework and national infection prevention and control policy, a number of implementation barrier persisted: lack of legal codification of TB as an occupational disease; absence of regulations assigning specific responsibilities to employers; failure to deal with privacy and stigma fears among health workers; and limited awareness among health workers of their legal rights, including that of collective action. While all these elements require attention to protect health workers from occupational TB, a stronger emphasis on their human and labour rights is needed alongside their perceived responsibilities as caregivers.

Empowering Health Workers to Protect Their Own Health: A Study of Enabling Factors and Barriers to Implementing HealthWISE in Mozambique, South Africa, and Zimbabwe.

Ways to address the increasing global health workforce shortage include improving the occupational health and safety of health workers, particularly those in high-risk, low-resource settings. The World Health Organization and International Labour Organization designed HealthWISE, a quality improvement tool to help health workers identify workplace hazards to find and apply low-cost solutions. However, its implementation had never been systematically evaluated. We, therefore, studied the implementation of HealthWISE in seven hospitals in three countries: Mozambique, South Africa, and Zimbabwe. Through a multiple-case study and thematic analysis of data collected primarily from focus group discussions and questionnaires, we examined the enabling factors and barriers to the implementation of HealthWISE by applying the integrated Promoting Action on Research Implementation in Health Services (i-PARiHS) framework. Enabling factors included the willingness of workers to engage in the implementation, diverse teams that championed the process, and supportive senior leadership. Barriers included lack of clarity about how to use HealthWISE, insufficient funds, stretched human resources, older buildings, and lack of incident reporting infrastructure. Overall, successful implementation of HealthWISE required dedicated local team members who helped facilitate the process by adapting HealthWISE to the workers' occupational health and safety (OHS) knowledge and skill levels and the cultures and needs of their hospitals, cutting across all constructs of the i-PARiHS framework.

From general toxicology to DNA disruption: A safety assessment of Plinia cauliflora (Mart.) Kausel.

ETHNOPHARMACOLOGICAL RELEVANCE: Plinia cauliflora (Mart.) Kausel (Myrtaceae) is popularly known as "jaboticaba" or "jaboticaba". The fruit is appreciated for both fresh consumption and the manufacture of jelly, juice, ice cream, fermented beverages, and liqueurs. The more widespread traditional use of the plant involves the treatment of diarrhea, which utilizes all parts of the plant, including the fruit peels. AIM OF THE STUDY: We sought to elucidate possible risks of the administration of an ethanol-soluble fraction that was obtained from an infusion of P. cauliflora fruit peels (SEIPC). We performed a series of experiments to evaluate possible toxicity, in which we administered SEIPC orally both acutely and repeatedly for 28 days. We also evaluated possible endocrine-disruptive and genotoxic effects in eukaryotic cells. The possible mutagenic activity of SEIPC was evaluated using reverse mutation (Ames) assays. MATERIALS AND METHODS: SEIPC was produced and chemically characterized by LC-DAD-MS. Acute toxicity and behavioral and physiological alterations were evaluated in the modified Irwin test. Respiratory rate, arterial blood gas, electrocardiography, respiratory rate, heart rate, and blood pressure were evaluated, and hematological, biochemical, and histopathological analyses were performed after 28 days of oral treatment. The comet assay, mammalian erythrocyte micronucleus test, uterotrophic test, Hershberger bioassay, and AMES test were performed using appropriate protocols. RESULTS: From SEIPC, ellagic acid and derivatives, flavonols and anthocyanidins, as well as citric acid and gallic acid, were annotated by LC-DAD-MS. We did not observed any significant toxic effects after acute or prolonged SEIPC treatment. No endocrine-disruptive or mutagenic effects were observed. CONCLUSIONS: The present study found that SEIPC did not cause any significant alterations of various corporeal systems, including cardiac electrical activity, body temperature, respiratory rate, and arterial pressure. No alterations of biochemical, hematological, or blood gas parameters were observed. SEIPC did not cause any perturbations of the endocrine system or mutagenic, cytotoxic, or genotoxic effects. These findings substantiate the safe clinical use of P. cauliflora.

Development of a Predictive Model to Induce Atherogenesis and Hepato-Renal Impairment in Female Rats.

Therapeutic approaches for the treatment of dyslipidemia and atherosclerosis have radically changed in recent decades. Part of this advance undeniably stems from basic biomedical research that has provided a better understanding and identification of new therapeutic targets. The aim of this work was to develop a model to induce atherogenesis and hepato-renal impairment in female Wistar rats. The following groups received the respective treatments for 60 days: control animals, non-ovariectomized rats that received an atherogenic diet (NEAD), ovariectomized rats that received an atherogenic diet (NOAD), non-ovariectomized rats that received an atherogenic diet and oral Nω-nitro-l-arginine methyl ester hydrochloride (l-NAME; LEAD), and ovariectomized rats that received an atherogenic diet and oral l-NAME (LOAD). Animals in the NEAD, NOAD, LEAD, and LOAD groups also received methimazole and cholecalciferol daily. Urinary, biochemical, hemodynamic, and electrocardiographic parameters and renal function were assessed. Samples of the liver, heart, kidney, and arteries were collected to investigate redox status and perform histopathological analyses. All of the groups developed dyslipidemia and hepatic steatosis. Only the NEAD group developed arterial lesions that were compatible with fatty streaks. Renal function was significantly impaired in the LEAD and NOAD groups. These results indicate a viable alternative to induce atherogenesis and hepato-renal impairment in female rats.

Pharmacological safety of Plinia cauliflora (Mart.) Kausel in rabbits.

Fruit peels of Plinia cauliflora (Mart.) Kausel are widely used in Brazilian traditional medicine, but no studies have proved the safety of its pharmacological effects on the respiratory, cardiovascular, and central nervous systems. The present study assessed the safety pharmacology of P. cauliflora in New Zealand rabbits. First, an ethanol extract (EEPC) was selected for the pharmacological experiments and chemical characterization. Then, different groups of rabbits were orally treated with EEPC (200 and 2000 mg/kg) or vehicle. Acute behavioral and physiological alterations in the modified Irwin test, respiratory rate, arterial blood gas, and various cardiovascular parameters (i.e., heart rate, blood pressure, and electrocardiography) were evaluated. The main secondary metabolites that were identified in EEPC were ellagic acid, gallic acid, O-deoxyhexosyl quercetin, and the anthocyanin O-hexosyl cyanidin. No significant behavioral or physiological changes were observed in any of the groups. None of the doses of EEPC affected respiratory rate or arterial blood gas, with no changes on blood pressure or electrocardiographic parameters. The present study showed that EEPC did not cause any significant changes in respiratory, cardiovascular, or central nervous system function. These data provide scientific evidence of the effects of this species and important safety data for its clinical use.

Cardioprotective effects of Plinia cauliflora (Mart.) Kausel in a rabbit model of doxorubicin-induced heart failure.

ETHNOPHARMACOLOGICAL RELEVANCE: In Brazil, the fruit of a native species that is popularly known as "jabuticaba" (Plinia cauliflora [Mart.] Kausel) is widely consumed fresh or used for the production of liqueur, juice, and jelly. In Brazilian folk medicine, this species is used to treat asthma, throat inflammation, and gastrointestinal and cardiovascular disturbances. However, no previous studies have reported its cardioprotective effects. AIM: To evaluate the possible cardioprotective effects of a hydroethanolic extract of Plinia cauliflora (EEPC) in female rabbits in a model of doxorubicin-induced heart failure. MATERIAL AND METHODS: EEPC was obtained and fractionated by solid phase extraction, and its constituents were determined by liquid chromatography coupled to diode array detector and mass spectrometry (LC-DAD-MS). Thirty female New Zealand rabbits received doxorubicin administration for 6 weeks to induce heart failure. EEPC was orally administered at doses of 75 and 150 mg/kg daily for 42 days. Enalapril (5 mg/kg) was used as a reference cardioprotective drug. At the end of the experimental period, blood pressure and heart rate were recorded. Serum parameters, including lipid profile, troponin, creatinine, nitrotyrosine, malondialdehyde, nitrite, and brain natriuretic peptide, were measured. The electrocardiographic profile and renal vascular reactivity were evaluated. Cardiac histopathology and ventricular morphometry were performed, and the tissue enzymatic antioxidant system was investigated. RESULTS: A total of 37 compounds were detected in EEPC, including organic acids, phenolic acid derivatives, flavonoids, anthocyanins, and hydrolysable tannins (gallotannins and ellagitannins). EEPC treatment induced a cardiorenal protective response, prevented hemodynamic and functional alterations, and prevented ventricle remodeling. These effects were associated with the normalization of creatinine and brain natriuretic peptide levels and modulation of the tecidual antioxidant defense system. CONCLUSION: The present study demonstrated that EEPC may prevent doxorubicin-induced heart failure by modulating the antioxidant defense system, reducing reactive oxygen species-induced damage, preventing alterations of hemodynamic and endothelial function, and preventing damage to the cardiac structure. EEPC, especially at the highest dose tested, may be considered a cardioprotective coadjuvant to prevent doxorubicin-induced cardiotoxicity.

Elderly patients on chronic hemodialysis with hyperparathyroidism: increase of hemoglobin level after intravenous calcitriol.

In patients on chronic hemodialysis (CHD), hyperparathyroidism (HPTH) is associated with anemia and resistance to erythropoietin (EPO). In the last few years, calcitriol intravenously (IV) has been used with success in the treatment of the HPTH, secondary to chronic renal failure. However, the effects of calcitriol on the hematological parameters of these patients have never been well evaluated. This study included 11 elderly CHD patients (f = 6, m = 5; mean age = 73.6 years, mean time on CHD = 42.8 months) with HPTH under EPO therapy (IV). They were treated for 12 months with calcitriol IV (mean dose = 2.33 mcg/pt/week). Patients with iron deficiency anemia (ferritin < 200 ng/ml) were excluded. The patients were compared before and after 12 months of calcitriol treatment, with respect to several laboratory parameters and with respect to EPO dose. A paired t-test was used. After treatment, we found a decrease of PTH (634 vs. 418 pg/ml, P = 0.029); the serum calcium increased (8.8 vs. 9.9 mg/dl, P = 0.002); no differences were noted in the plasma levels of alkaline phosphatase, phosphorous, BUN, creatinine, Na and K. Mean levels of Hb (10.2 vs. 11.4 g/dl, P = 0.004) and the Hct (30 vs. 34.3, P = 0.004) increased after 12 months of calcitriol; the levels of serum iron (70 vs. 78 microg/dl, P = ns) and ferritin (531 vs. 785 ng/ml, P = ns) and the EPO dose (105 vs. 100 U/kg/week, P = ns) were similar before and after treatment. Our data show that the treatment of HPTH in CHD elderly patients with calcitriol can increase Hb level without increasing EPO dose.

Elderly patients on chronic hemodialysis: effect of the secondary hyperparathyroidism on the hemoglobin level.

In patients on chronic hemodialysis (CHD) hyperparathyroidism (HPTH) is associated with anemia and resistance to erythropoietin (EPO). This study included 86 CHD elderly pts (mean age 74.8 y, mean time on CHD = 50.5 mos); they were divided into two groups: I (n = 31) - PTH > 250 pg/mL and II (n = 55) - PTH < 250 pg/mL. All these patients had been on CHD for > 6 mos. No differences were found between groups in respect to age, sex distribution and time on CHD. The levels of creatinine, BUN, Ca, Al, Fe, albumin and ferritin were similar. Group I had a higher P level (5.4 vs 4.3 mg/dL, p = 0.001) and Ca x P (53.5 vs 43.7, p = 0.009). Also the Hct (31 vs 33.5%, p = 0.008) and the Hb (10.4 vs 11.2 g/dL, p = 0.009) values were lower in Group I. The EPO dose (88 vs 85 U/kg/week, p = ns) was similar in the two groups. Our data showed that elderly patients with HPTH have lower Hct and Hb levels than do younger patients on a similar EPO dose. We believe these patients will need a more aggressive therapy with calcitriol.