Angiotensin II increases parathyroid hormone-related protein (PTHrP) and the type 1 PTH/PTHrP receptor in the kidney

Angiotensin II (AngII) participates in the pathogenesis of kidney damage. Parathyroid hormone (PTH)-related protein (PTHrP), a vasodilator and mitogenic agent, is upregulated during renal injury. The aim of this study was to investigate the potential relation between AngII and PTHrP system in the kidney. Different methods were used to find that both rat mesangial and mouse tubuloepithelial cells express PTHrP and the type 1 PTH/PTHrP receptor (PTH1R). In these cells, AngII increased PTHrP mRNA and protein production. In contrast, PTH1R mRNA was increased in mesangial cells and downregulated in tubular cells, but its protein levels were unmodified in both cells. AT(1) antagonist, but not AT(2), abolished AngII effects on PTHrP/PTH1R. The in vivo effect of AngII was further investigated by systemic infusion (a low dose of 50 ng/kg per min) into normal rats. In controls, PTHrP immunostaining was mainly detected in renal tubules. In AngII-infused rats, PTHrP staining increased in renal tubules and appeared in the glomerulus and the renal vessels. After AngII infusion, PTHR1 staining was markedly increased in all these renal structures at day 3 but remained elevated only in tubules at day 7. The AT(1) antagonist, but not the AT(2), significantly diminished AngII-induced PTHrP and PTHR1 overexpression in the renal tissue, associated with a decrease in tubular damage and fibrosis. The results indicate that AngII regulates renal PTHrP/PTH1R system via AT(1) receptors. These findings demonstrate that PTHrP upregulation occurs in association with the mechanisms of AngII-induced kidney injury.     

Breast cancer management in middle-resource countries (MRCs): consensus statement from the Breast Health Global Initiative

In middle resource countries (MRCs), cancer control programs are becoming a priority as the pattern of disease shifts from infectious diseases to non-communicable diseases such as breast cancer, the most common cancer among women in MRCs. The Middle Resource Scenarios Working Group of the BHGI 2010 Global Summit met to identify common issues and obstacles to breast cancer detection, diagnosis and treatment in MRCs. They concluded that breast cancer early detection programs continue to be important, should include clinical breast examination (CBE) with or without mammography, and should be coupled with active awareness programs. Mammographic screening is usually opportunistic and early detection programs are often hampered by logistical and financial problems, as well as socio-cultural barriers, despite improved public educational efforts. Although multidisciplinary services for treatment are available, geographical and economic limitations to these services can lead to an inequity in health care access. Without adequate health insurance coverage, limited personal finances can be a significant barrier to care for many patients. Despite the improved availability of services (surgery, pathology, radiology and radiotherapy), quality assurance programs remain a challenge. Better access to anticancer drugs is needed to improve outcomes, as are rehabilitation programs for survivors. Focused and sustained government health care financing in MRCs is needed to improve early detection and treatment of breast cancer.     

Integrated treatment of secondary hepatolithiasis. Case report

Hepatolithiasis is defined as the occurrence of stones proximal to the biliary confluence and represents a prevalent disease in South East Asia being uncommon in Western countries. Biliary sepsis, hepatic abscesses and cholangiocarcinoma are considered potential complications. The Authors describe a case of a 68 years male patient affected by a left massive intrahepatic lithiasis secondary to common duct stones and associated to acute pancreatitis. The patient refused surgery and was submitted to a conservative transhepatic percutaneous treatment. After a complete removal of intrahepatic stones and a positioning of external internal biliary drainage (14F), a laparoscopic cholecistectomy was performed. The MRI control showed a complete resolution of the intrahepatic lithiasis. Conservative transhepatic percutaneous approach to hepatolithiasis represents a safe and effective treatment allowing good medium-long term results. Surgery is recommended in case of severe hepatic fibrosis or atrophy, suspected cholangiocarcinoma or multiple strictures with biliary distorsion. Integrated therapeutical protocols in referral multidisciplinary centers-offers the best long term results.     

Surgical treatment of Basedow's disease: our experience with 424 operations

From February 2002 to December 2005, 424 operations for thyroid disease were performed in our institute. Twenty-two patients were suffering from Basedow's disease, 14 female and 8 male, mean age 36 years (range: 23 to 53 years). In each patient the diagnosis of Basedow's disease was made according to common clinical and laboratory criteria, by evaluation of the thyroid hormones, TSH and TRAB. Before operation all patients were rendered euthyroid with antithyroid drug treatment. Fourteen total thyroidectomies (64%) and 8 near-total thyroidectomies (36%) were performed. Postoperative thyroid function status was evaluated before, 3-4 weeks after the operation and then 3, 6,12 and 24 months postoperatively. The patients were classified as euthyroid (FT3-FT4 and TSH normal), hypothyroid (FT3 and/or FT4 reduced and TSH increased), or hyperthyroid (FT3-FT4 increased). In expert hands, surgical treatment appears to be capable of curing the hyperthyroidism of Basedow's disease effectively, with a very low and largely acceptable risk of complications. Among the different types of surgery, total thyroidectomy and near-total thyroidectomy are equally appropriate to ensure there is no risk of recurrence of hyperthyroidism.     

Evaluation of methods based on creatinine and cystatin C to estimate glomerular filtration rate in chronic kidney disease

Purpose

Estimated glomerular filtration rate (GFR) is a useful tool for the detection of chronic kidney disease (CKD). Several methods have been proposed, but findings can vary in specific groups such as patients with diabetes, elderly and high and low body mass index and, also, with the stage of CKD. The objective of this study was comparing the accuracy of the currently used equations for estimating GFR with that of the gold standard technetium-(99m)-diethylene triamine pentaacetic acid (99mTc-DTPA).

Methods

We performed a cross-sectional study of 129 patients with all five CKD stages. GFR was estimated using the following: 24-h urine creatinine clearance, Cockcroft–Gault equation, MDRD equation, CKD-EPI equation, Hoek’s cystatin C equation, and isotopic 99mTc-DTPA (as gold standard). We evaluated agreement in the whole study population and according to age, sex, weight, and diabetes.

Results

All methods had good agreement. The best agreement was observed with the cystatin C [intraclass coefficient correlation (ICC) 95 % confidence interval (95 % CI), 0.87 (0.82–0.91)], followed by CKD-EPI [ICC 0.83 (0.77–0.88)]. Twenty-four-hour urine creatinine clearance showed the worst agreement in patients older than 65 years [ICC 0.70 (0.56–0.79)]. The Cockcroft–Gault equation showed the worst agreement in younger than 65 years [ICC 0.64 (0.42–0.79)]. The best agreement for classification in the correct CKD stage was with the cystatin C equation [κ = 0.80 (0.74–0.87)]. GFR was overestimated with all methods in CKD stages 4 and 5.

Conclusions

The methods used in clinical practice are adequate for classification of CKD. Cystatin C is the most accurate method, followed by CKD-EPI. The Cockcroft–Gault equation is not accurate in young patients. Twenty-four-hour urine creatinine clearance loses accuracy in patients aged older than 65 years.     

Atypical antioxidant activity of non-phenolic amino-coumarins

Coumarin compounds have been described as anti-inflammatories, and chemotherapeutic agents as well as antioxidants. However, the origin of the antioxidant activity of non phenolic coumarins remains obscure. In the present report, we demonstrate that non-phenolic 7-dialkyl-aminocoumarins may also have significant antioxidant properties against free radicals derived from 2,2′-azobis(2-amidinopropane) dihydrochloride under aerobic conditions. This atypical behaviour is due to the presence of traces of very reactive hydroxycinnamic acid-type compounds. Changing functional groups at the C-3 and C-4 positions shifts the reactivity of the compounds from peroxyl to alkoxyl free radicals. Kinetic and theoretical studies based on Density Functional Theory support the formation of reactive hydroxycinnamic acid and directly link the antioxidant behaviour of the compounds to hydrogen atom transfer.

Relevant antioxidant properties of non-phenolic 7-dialkyl-aminocoumarins against free radicals derived from 2,2′-azobis(2-amidinopropane) dihydrochloride under aerobic conditions have been experimentally and theoretically demonstrated.     

Effectiveness of pirmenol hydrochloride in suppressing high frequency ventricular ectopy: a placebo-controlled, double-blind, multicenter study

An 8-center European clinical trial has established that pirmenol in dosages up to 400 mg daily is effective and safe for treating stable, high frequency, ventricular ectopy. At dosages of 300 mg and 400 mg of pirmenol a day, the average frequency of ectopy/hour decreased markedly compared with baseline values. The percentage of responders (premature ventricular contraction suppression of 70% compared with baseline) among the patients receiving 300 mg or 400 mg of pirmenol/day was significantly higher than in the placebo group. Observation of the frequency of reported adverse experiences, clinical laboratory tests and electrocardiographic tracings shows that dosages of pirmenol up to 400 mg daily were well tolerated.