High renin hypertension in focal renal fibromuscular dysplasia: turn off of renin system angiotensin overactivation by renal angioplasty cured high blood pressure and quickly reversed myocardial hypertrophy.

Background Fibromuscolar dysplasia (FMD) is an idiopathic, non-atherosclerotic and non-inflammatory stenotic lesion of renal arteries causing renovascular hypertension up-regulating renin-angiotensin-aldosterone system. Case report: A 18-year-old man was referred to our Hypertension Center (Clinica e Terapia Medica) for the recent onset of hypertension, poorly controlled on calcium channel blockers, already associated to electrocardiographic and echocardiography signs of left ventricular hypertrophy and significant albuminuria (728 mg/24 h). An increased plasma renin activity (PRA), aldosterone level and a mild hypokalemia raised the suspicion of renovascular hypertension. Abdominal CT and MRI angiography showed mild kidneys asymmetry and a tubular stenosis of the right renal artery in its mid-distal portion close to renal hilum. Radionuclide renal scintigraphy documented a kidneys asymmetry of separated glomerular filtration rate. Renal FMD was diagnosed based on patient age and the absence of cardiovascular risk factors for atherosclerosis. Patient successfully underwent right renal angioplasty giving a rapid normalization of blood pressure levels without antihypertensive drugs. Plasma aldosterone and PRA rapidly normalized as well as serum potassium levels. Six months after angioplasty echocardiography showed a regression of left ventricular hypertrophy and the patient albumin urine excretion became normal (14 mg/24 h). Conclusions FMD can cause renovascular hypertension associated to organ damage such myocardial hypertrophy and albuminuria through mechanisms dependent but also independent from blood pressure levels. Renal angioplasty turned off renin-angiotensin-aldosterone overactivity allowing the cure the hypertension and a surprisingly rapid reverse of myocardial hypertrophy and of excess of albumin urine excretion not only dependent on blood pressure normalization.

Electrolyte Disorders Induced by Antineoplastic Drugs.

The use of antineoplastic drugs has a central role in treatment of patients affected by cancer but is often associated with numerous electrolyte derangements which, in many cases, could represent life-threatening conditions. In fact, while several anti-cancer agents can interfere with kidney function leading to acute kidney injury, proteinuria, and hypertension, in many cases alterations of electrolyte tubular handling and water balance occur. This review summarizes the mechanisms underlying the disturbances of sodium, potassium, magnesium, calcium, and phosphate metabolism during anti-cancer treatment. Platinum compounds are associated with sodium, potassium, and magnesium derangements while alkylating agents and Vinca alkaloids with hyponatremia due to syndrome of inappropriate antidiuretic hormone secretion (SIADH). Novel anti-neoplastic agents, such as targeted therapies (monoclonal antibodies, tyrosine kinase inhibitors, immunomodulators, mammalian target of rapamycin), can induce SIADH-related hyponatremia and, less frequently, urinary sodium loss. The blockade of epidermal growth factor receptor (EGFR) by anti-EGFR antibodies can result in clinically significant magnesium and potassium losses. Finally, the tumor lysis syndrome is associated with hyperphosphatemia, hypocalcemia and hyperkalemia, all of which represent serious complications of chemotherapy. Thus, clinicians should be aware of these side effects of antineoplastic drugs, in order to set out preventive measures and start appropriate treatments.

Posterior reversible encephalopathy syndrome in an oncological normotensive patient: evidence for a pathogenic role of concomitant low magnesium serum levels and chemotherapy treatment.

BACKGROUND: Posterior reversible encephalopathy (PRES) is a rare syndrome characterized by headache, confusion, seizures, visual changes and white matter edema at radiological imaging. Its pathophysiology is not clarified and different causes, including uncontrolled hypertension, eclampsia, chemotherapy and hypomagnesemia have been suggested. CASE REPORT: A woman affected by stage IV breast cancer with lower extremity deep vein thrombosis treated with low-molecular-weight-heparin, currently in therapy with Palbociclib/Fulvestrant (antiCDK4 and 6/estrogen receptor antagonist) but previously treated with several other chemotherapy lines (including VEGF inhibitor bevacizumab), was admitted to our Internal Medicine department because of ascites and abdominal pain. She was treated with diuretics (and paracentesis). Recently (six-month earlier) a pan-encephalic radiotherapy was done because of brain and skull metastasis. Among blood tests, low serum levels of hypomagnesemia were observed. She developed PRES that rapidly progressed to lethargy, unresponsiveness till coma without changes in blood pressure. Magnetic Resonance Imaging study showed bilateral parieto-occipital edema and a thrombosis of left transverse and sigmoid sinuses. Anti-edema therapy, intravenous supplementation of magnesium and decoagulation were started, with complete and rapid recovery (within 18 hours) of clinical and radiologic changes. CONCLUSIONS: PRES diagnosis was based on the rapid clinical recovery after antiedema treatment and magnesium supplementation. Low magnesium level related to both diuretic and Fulvestrant/Palbociclib therapies and recent radiotherapy can represent potential mechanisms favouring PRES development. The previous bevacizumab treatment may also be involved as a PRES predisposing factor. The concomitant occurrence of cerebral thrombosis can have precipitated the clinical situation.

Notch1 Pathway Activity Determines the Regulatory Role of Cancer-Associated Fibroblasts in Melanoma Growth and Invasion.

Cancer-associated fibroblasts (CAF) play a crucial role in regulating cancer progression, yet the molecular determinant that governs the tumor regulatory role of CAF remains unknown. Using a mouse melanoma model in which exogenous melanoma cells were grafted on the skin of two lines of mice where the genetic activation or inactivation of Notch1 signaling specifically occurs in natural host stromal fibroblasts, we demonstrated that Notch1 pathway activity could determine the tumor-promoting or tumor-suppressing phenotype in CAF. CAF carrying elevated Notch1 activity significantly inhibited melanoma growth and invasion, while those with a null Notch1 promoted melanoma invasion. These findings identify the Notch1 pathway as a molecular determinant that controls the regulatory role of CAF in melanoma skin growth and invasion, unveiling Notch1 signaling as a potential therapeutic target for melanoma and potentially other solid tumors.

Sildenafil counteracts the inhibitory effect of social subordination on competitive aggression and sexual motivation in male mice.

The effects of chronic intra-peritoneal administration of 10 mg/kg (t.i.w., for 5 weeks) of sildenafil on competitive aggression, sexual behaviour and body weight gain was tested in CD1 subordinate male mice in two experimental contexts: 1) "low levels of aggression", i.e. housing in dyads of siblings 2) "high levels of aggression", i.e. exposure to a model of chronic psychosocial stress with an unfamiliar mice. Subordinate mice in both experimental contexts were injected with sildenafil or saline. After 2 weeks of sildenafil administration, a subgroup of subordinates exposed to "high levels of aggression" began to counterattack their dominant counterparts at higher rates than saline-injected subordinates. This effect was essentially similar but faster in subordinates subjected to "low levels of aggression". As far as sexual behaviour is concerned, in both experimental contexts, sildenafil-injected subordinated mice showed significant lower latencies to mount a proceptive female when compared to saline-injected subjects. Furthermore, in the "high levels of aggression" context, Sildenafil reduced stress-induced body weight gain. Sildenafil showed no effects in individually housed males serving as controls. In conclusion, chronic Sildenafil treatment counteracts the inhibitory effects of social subordination on male competitive aggression, sexual behaviour and body weight gain. Overall our data suggests that sildenafil could be acting in the central nervous system to modulate sexual and agonistic motivation.