Zaher Armaly

Corin: a new player in the regulation of salt-water balance and blood pressure.

Purpose of reviewNatriuretic peptides play a key role in regulation of blood pressure and volume homeostasis due to their natriuretic/diuretic and vasodilatory actions. The natriuretic and diuretic responses to natriuretic peptides are markedly attenuated in edematous disease states. Our goal is to review the mechanisms underlying this phenomenon, with special emphasis on the role of corin in salt retention and edema formation in heart failure and nephrotic syndrome, and pathogenesis of hypertension. Recent findingsAlthough three decades have passed since the discovery of atrial natriuretic peptide (ANP), major advances in understanding the physiological and pathophysiological role of the natriuretic peptide family in the regulation of sodium (Na+) and water balance are still emerging. As well as ANP, the natriuretic peptide family contains at least two other members: brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP). Although encoded by different genes, these natriuretic peptides share a high similarity in their chemical structure and biosynthesis pathway. ANP and BNP are produced from proANP and proBNP, respectively, which are converted into the active forms mainly by corin. The latter is a transmembrane serine protease localized to the heart, and to a lesser extent to the kidneys. Recent studies have demonstrated that perturbations in corin activity lead to elevation of the prohormones at the expense of the mature forms, thereby causing the development of salt-sensitive hypertension, preeclampsia, cardiac hypertrophy, and Na+ and water retention. SummaryNatriuretic peptides are an important endocrine system in the regulation of body fluid balance and blood pressure. Corin mediates an essential step in the cascade of natriuretic peptide biosynthesis and eventually their action. Thus, it is postulated that aberrations in the normal activity of corin may contribute to cardiovascular and renal diseases.

Phosphodiesterase-5 inhibition attenuates early renal ischemia-reperfusion-induced acute kidney injury: assessment by quantitative measurement of urinary NGAL and KIM-1.

Acute kidney injury (AKI) is a common clinical problem that still lacks effective treatment. Phosphodiesterase-5 (PDE5) inhibitors possess anti-apoptotic and anti-oxidant properties, making it a promising therapy for ischemia-reperfusion (I/R) injury of various organs. The present study evaluated the early nephroprotective effects of Tadalafil, a PDE5 inhibitor, in an experimental model of renal I/R. Sprague-Dawley rats were divided into two groups: vehicle-treated I/R (n = 10), and Tadalafil (10 mg/kg po)-treated I/R group (n = 11). After removal of the right kidney and collection of two baseline urine samples, the left renal artery was clamped for 45 min followed by reperfusion for 60, 120, 180, and 240 min. Functional and histological parameters of the kidneys from the various groups were determined. In the vehicle-treated I/R group, glomerular filtration rate was significantly reduced compared with that in normal kidneys. In addition, the ischemic kidney showed remarkable cast formation, necrosis, and congestion, a consistent pattern of acute tubular necrosis. Furthermore, urinary excretion of NGAL and KIM-1, two novel biomarkers of kidney injury, substantially increased following I/R insult. In contrast, Tadalafil treatment resulted in a significant improvement in kidney function and amelioration of the adverse histological alterations of the ischemic kidney. Noteworthy, the urinary excretion of NGAL and KIM-1 markedly decreased in the Tadalafil-treated I/R group. These findings demonstrate that Tadalafil possesses early nephroprotective effects in rat kidneys subjected to I/R insult. This approach may suggest a prophylactic therapy for patients with ischemic AKI.

Neuropsychopharmacology and Neurogenetic Aspects of Executive Functioning: Should Reward Gene Polymorphisms Constitute a Diagnostic Tool to Identify Individuals at Risk for Impaired Judgment?

Executive functions are processes that act in harmony to control behaviors necessary for maintaining focus and achieving outcomes. Executive dysfunction in neuropsychiatric disorders is attributed to structural or functional pathology of brain networks involving prefrontal cortex (PFC) and its connections with other brain regions. The PFC receives innervations from different neurons associated with a number of neurotransmitters, especially dopamine (DA). Here we review findings on the contribution of PFC DA to higher-order cognitive and emotional behaviors. We suggest that examination of multifactorial interactions of an individual’s genetic history, along with environmental risk factors, can assist in the characterization of executive functioning for that individual. Based upon the results of genetic studies, we also propose genetic mapping as a probable diagnostic tool serving as a therapeutic adjunct for augmenting executive functioning capabilities. We conclude that preservation of the neurological underpinnings of executive functions requires the integrity of complex neural systems including the influence of specific genes and associated polymorphisms to provide adequate neurotransmission.

Major depressive disorders in chronic hemodialysis patients in Nazareth: identification and assessment

Objective Depression illnesses are commonly observed in hemodialysis (HD) patients, which can influence the quality of life of end-stage renal disease patients. We evaluate the prevalence and predictive risk factors of depression in the Arab population undergoing HD in Nazareth, Israel. Methods We conducted a prospective study that included 71 patients in the HD unit with a mean age of 61.9 ± 14.13 years who had undergone HD and 26 healthy control subjects with a mean age of 59.3 ± 7.3. Beck’s Depression Inventory and Hamilton Depression Scale assessments were administered. Blood analysis for hematological and biochemical parameters was obtained. Diagnosis was made using the Diagnostic and Statistical Manual of Mental Disorders scale to correlate psychological variables with clinical, hematological, and biochemical parameters. Statistical analysis was carried out using analysis of variance followed by Tukey post-hoc multiple comparison tests. Results The prevalence of depression was 43.7% in HD patients. Between HD patients and controls, cortisol values were 16.96 ± 0.5476 and 11.96 ± 1.116, respectively (P < 0.0001; 95% confidence intervals [CI]: 2.416–6.825). Between depressed HD patients versus control subjects, cortisol values were 16.48 ± 0.72 and 11.96 ± 1.116, respectively (P = 0.0013; 95% CI: 1.878–7.184). Hematological and biochemical parameters were compared between depressed HD and nondepressed patients, but differences between the two groups were found to be insignificant (P > 0.05). Conclusion Our HD patients were severely depressed. Studies of glucocorticoid turnover activity such as cortisol, a potent chemical stress hormone, may be used as a model and marker for early diagnosis of depression among HD patients. The strong familial support system in Arabic traditions has failed to decrease depression among these patients.

Phosphodiesterase 5 inhibition protects against increased intra-abdominal pressure-induced renal dysfunction in experimental congestive heart failure.

Congestive heart failure (CHF) is associated with impaired renal function. Previously, we have demonstrated that rats with decompensated CHF exhibited exaggerated sensitivity to the adverse renal effects of increased increased intra‐abdominal pressure (IAP) as compared with normal controls. This study tested whether phosphodiesterase 5 (PDE5) inhibition protects against the adverse renal effects of increased IAP in rats with CHF.

Nephroprotective effects of TVP1022, a non-MAO inhibitor S-isomer of rasagiline, in an experimental model of diabetic renal ischemic injury

Ischemic acute kidney injury (iAKI) in diabetes mellitus is associated with a rapid deterioration of kidney function, more than in nondiabetic subjects. TVP1022, a non-MAO inhibitor S-isomer of rasagiline, possesses antioxidative and antiapoptotic activities. The current study examines the effects of TVP1022 and tempol on iAKI in diabetic rats. Diabetes was induced by streptozotocin. iAKI was induced by clamping the left renal artery for 30 min in both diabetic and nondiabetic rats. The right intact kidney served as a control. Forty-eight hours following ischemia, urinary flow (V), sodium excretion (UNaV), and glomerular filtration rate (GFR) in both ischemic and nonischemic kidneys were determined. The nephroprotective effects of tempol and TVP1022 were examined in these rats. Hematoxylin and eosin staining, 4-hydroxynonenal (4-HNE) immunofluorescence, and nitrotyrosine immunohistochemistry were performed on renal tissues of the various experimental groups. Compared with normoglycemic rats, iAKI in diabetic animals caused more profound reductions in V, UNaV, and GFR. Tempol and TVP1022 treatment increased GFR two- and four-fold in diabetic ischemic kidney, respectively. Besides hemodynamic perturbations, iAKI markedly increased renal immunoreactive 4-HNE and nitrotyrosine staining in both diabetic and nondiabetic rats. Moreover, iAKI increased medullary necrosis, congestion, and casts. Noteworthy, these increases were to a larger extent in ischemic diabetic kidneys. TVP1022, and to a lesser extent tempol, decreased nitrotyrosine and 4-HNE immunoreactivities and necrosis and cast formation in the renal medulla. TVP1022 treatment improves renal dysfunction and histological changes in an iAKI diabetic model and suggests a role for TVP1022 therapy in kidney injury.

Maxillary and Frontal Bone Simultaneously Involved in Brown Tumor due to Secondary Hyperparathyroidism in a Hemodialysis Patient

Brown tumors are rare focal giant cell lesions of the bone caused by primary hyperparathyroidism (HPT). Brown tumor was reported in 1891; it presents as the end-stage findings of HPT. Common involvements are skull and pelvic girdle. We describe a case of 46-year-old female hemodialysis patient, with secondary HPT in whom multiple masses lesions of the left maxillary sinus and frontal bone were radiologically suspected to be brown tumor. This unusual manifestation of secondary HPT can be expected to occur with increased longevity of patients with renal failure and illustrates the need to include brown tumor in the differential diagnosis.

Non catheter-related bacteremia caused by Pseudomonas oryzihabitans in a patient undergoing hemodialysis

Pseudomonas oryzihabitans (P. orizyhabitans) has already been reported both as a human and a zoonotic pathogen. A few cases of P. orizyhabitans bacteremia have been reported among patients who underwent peritoneal dialysis. P. orizyhabitans bacteremia has never been reported among patients on hemodialysis. We report the first case of P. orizyhabitans bacteremia in a chronic hemodialysis patient; this patient did not have a central venous catheter angioaccess as a potential portal of entry.

Acute kidney injury following isotretinoin treatment

Patient: Female, 17 Final Diagnosis: Acute kidney injury Symptoms: Flank pain • nausea • vomiting Medication: Isotretinoin Clinical Procedure: Acne treatment Specialty: Nephrology Objective: Unknown etiology Background: Isotretinoin is widely used for the treatment of acne that is unresponsive to topical therapy. Despite its efficacy, isotretinoin has various adverse effects, including cheilitis, increased risk of cutaneous Staphylococcus aureus infections, and liver function abnormalities. Case Report: A 17-years-old female was admitted to the hospital with a 5-day history of bilateral flank pain, nausea and vomiting. On physical examination, acne was observed over her face treated with Isotretinoin. Both vital signs and physical examination were normal apart from tenderness over both flanks. Initial laboratory results revealed serum creatinine of 2 mg/dl, blood urea nitrogen 20 mg/dl. Complete blood count, full chemistry panel, complements and urinalysis were all normal. Twenty four hours urine collection showed creatinine clearance test of 33 ml/min and urine protein of 390 mg/day. Chest X-ray and ultra sound of kidneys were normal. Acute kidney injury was suspected and she was treated with intravenous fluids. Despite these measures her kidney function steadily worsened. Her serum creatinine on days 2 and 3 were 2.16 and 2.24 mg/dl, respectively. Wright’s staining for eosinophils was positive. Fortunately her serum creatinine started to decrease and was 2 mg/dl and 1.4 mg/dl by day 4 and 5, respectively. A tentative diagnosis of acute interstitial nephritis due to Isotretinoin was made, with the recommendation to avoid this treatment in the future. Two weeks later her serum creatinine and urinary protein returned to normal values. Conclusions: Flank pain should raise suspicion of Isotretinoin-induced acute kidney injury, suggesting that a careful kidney function test besides testing for liver function is warranted in patients with these symptoms.

Pharmacist counseling to cardiac patients in Israel prior to discharge from hospital contribute to increasing patient's medication adherence closing gaps and improving outcomes

BackgroundMedication non adherence is a global epidemic perplexing phenomenon that is eminent, but not insurmountable. Our first objective was to explore whether providing pharmacists counseling to cardiac patients prior to discharge can increase patients medication adherence, and our second objective was to assess whether better medication adherence leads to reduction of hospital readmissions.MethodsObservational study was conducted among diagnosed cardiac patients using an intervention strategy at discharge from two hospitals in Israel; The Nazareth and the Haemek hospital. 74 patients were recruited between January 2010 and January 2011. Two separate groups were selected; intervention group: 33 patients who prior to discharge received nurse, pharmacist interventions, and control group: 41 patients who had received the nurse and hospital discharge counseling only.ResultsRegression analysis for examining the first objective reflected significant effect when having a pharmacist interventions, which explains the increasing 11.6% of the variance in medication adherence, [F change (1,73) = 9.43, p < 0.003]. Stepwise regression analysis for examining the second objective demonstrated that the relation between medication adherence and readmissions was insignificant [F (1,73) = 9.43, n.s].ConclusionsWhile physicians and nurses can have an impact on improving adherence, pharmacists have demonstrated the ability to inform, problem-solve and provide performance support directly to patients.