A novel lab-scale screen extruder for studying extrusion-spheronisation.

A novel apparatus, the laboratory roller screen extruder (termed the LRS), was developed to replicate key aspects of the geometry and shear strain rates generated near the screen of industrial screen extruders. The configuration of the LRS is reported alongside a commissioning study employing a cohesive 45 wt% water/microcrystalline cellulose paste. The key operating parameters which controlled the extrudate mass flowrate, force on the screen and roller torque were (i) the size of the gap between the top of the roller blade and the screen, and (ii) the roller rotational speed. The data suggest that the apparent shear rate, based on the blade-screen clearance, provides a quantitative criterion for scale-up. The amount of screen flex showed good agreement with a simple bending deformation model. Spheronisation of the extrudates gave pellets with a narrow size distribution and acceptable sphericity which would be acceptable for capsule filling. Optimisation of the pellet shape was not performed. The results indicate that the LRS can be used to assess formulations for industrial screen extrusion-spheronisation.

Extrusion-spheronisation of microcrystalline cellulose pastes using a non-aqueous liquid binder.

An experimental investigation of extrusion-spheronisation (E-S) of a novel microcrystalline cellulose (MCC) formulation, comprising dimethyl sulfoxide (DMSO) as the granulating liquid, is reported. The extrusion-spheronisation performance of DMSO/MCC pastes is compared to that of similar water/MCC formulations and their rheological behaviours similarly assessed using lubricated squeeze flow. A case study involving water, DMSO and anhydrous ethanol yields important information regarding the physico-chemical properties necessary for solvents to be suitable for the extrusion of MCC.

Ischemic steal syndrome in a hemodialysis patient: The roles of Doppler ultrasonography and dynamic Doppler studies in diagnosis and treatment selection.

Ischemic steal syndrome (ISS) is a complication that can occur after the construction of a vascular access for hemodialysis. It is characterized by ischemia of the hand caused by marked reduction or reversal of flow through the arterial segment distal to the arteriovenous fistula (AVF). The diagnosis of hand ischemia is based on physical examination, but imaging studies are very useful for detecting the true cause of ischemia and for selecting an appropriate therapeutic strategy. In this report, we describe an uncommon cause of ISS in a patient on hemodialysis. The ischemia was caused by the presence of undetected flow through an older AVF on the same arm as the AVF used for dialysis. The unsuspected "steal" was disclosed by color Doppler examination of the vascular bed of the patient's left arm. Dynamic Doppler studies then played a fundamental role in the decision to ligate the distal radio-cephalic AVF. The procedure led to the complete relief of ischemic symptoms.

[Treatment of HCV-associated cryoglobulinemic glomerulonephritis]. / Terapia della glomerulonefrite secondaria a crioglobulinemia HCV-correlata.

HCV-related membranoproliferative glomerulonephritis is the most common cause of hepatitis C-associated renal disease. Its treatment is still under debate and based on scant experimental evidence. The recommended therapeutic strategy depends on the severity of the kidney disease. The first-line treatment for patients with mild to moderate clinical and histological kidney damage is antiviral therapy with pegylated interferon alpha and ribavirin for 48 weeks combined with symptomatic treatment (diuretics, angiotensin converting enzyme inhibitors and angiotensin receptor blockers). In case of severe renal involvement (nephrotic syndrome, nephritic syndrome and/or progressive renal failure, high activity score of glomerulonephritis on light microscopy), the initial treatment may consist of sequential administration of immunosuppressive therapies (plasmapheresis, corticosteroids and cyclophosphamide) and antiviral agents, although no definitive data are yet available from the literature. B-cell depleting agents such as rituximab may be an alternative to conventional therapy in refractory or intolerant patients. Large randomized and controlled clinical trials are needed to establish guidelines for the treatment of HCV-related cryoglobulinemic glomerulonephritis.

[Hyponatremia secondary to inappropriate antidiuretic hormone secretion]. / Iposodiemia da inappropriata secrezione di ADH.

The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is a disorder of sodium and water balance characterized by hypotonic hyponatremia and impaired water excretion in the absence of renal insufficiency , adrenal insufficiency or any recognized stimulus for the antidiuretic hormone (ADH). An inappropriate increase in ADH release of any cause produces hyponatremia by interfering with urinary dilution, thereby preventing the excretion of ingested water. Despite being the most common cause of hyponatremia in hospitalized patients, SIADH remains a diagnosis of exclusion. SIADH should be suspected in any patient with hyponatremia, hyposmolarity, urine osmolality above 100 mosmol/hgH2O, urine sodium concentration usually above 40 mEq/L, and clinical euvolemia. a number of modalities can be used to correct hyponatremia in SIADH, with water restriction and salt administration being the most important. The rate of correction is dependent upon the degree of hyponatremia and the presence or absence of symptoms. Patients with severe neurological symptoms require prompt correction; however, excessively rapid correction should be avoided because it can lead to the late onset of neurological complications from osmotic demyelination.

Liquid phase migration in the extrusion and squeezing of microcrystalline cellulose pastes.

Extensive movement of the liquid phase relative to the solids in solid-liquid pastes during extrusion forming is an undesirable process phenomenon. The impact of formulation and flow pattern on liquid phase migration (LPM) during extrusion of model pharmaceutical pastes (40-50 wt% microcrystalline cellulose/water) has been investigated by ram extrusion through square-entry and 45 degrees conical-entry dies, and by lubricated squeeze flow (extensional flow). Threshold velocities for LPM were observed in both configurations. Squeeze flow testing showed that dilation during extension can cause LPM, while ram extrusion featured both dilation effects and drainage due to compaction. The threshold velocities observed in the two configurations agreed when presented as characteristic shear rates. The threshold velocity increased with paste solids content.

[Hypertension in patients on hemodialysis: the role of salt intake]. / L'ipertensione arteriosa nell'uremico in emodialisi: importanza dell'intake di sale.

In the 1960s, about 10% of hemodialysis (HD) patients had hypertension; the current percentage of hypertensive patients has risen to 70-75%. The scarce implementation of low-salt diets and the increment of dialysate sodium concentration aimed at ameliorating treatment tolerability are the main causes of the currently poor hypertension control. Considerable sodium intake activates a vicious circle: an increase in serum osmolarity, greater thirst and greater water intake, high inter-dialytic weight gains, need for large ultrafiltration rates, more frequent episodes of intradialytic hypotension, failure to achieve dry weight, progressive extra-cellular volume (ECV) expansion, and finally, blood pressure (BP) increase. Therefore, many studies have pointed out the importance of a low-salt diet in HD; it has been proven that the normalization of BP and ECV overload with a low-salt diet is associated with left ventricular hypertrophy regression and diastolic dysfunction improvement. Preparing meals with fresh foods, using spices, avoiding salt when cooking, and drastically limiting salty foods reduce dietary sodium down to about 6 g/day. Sodium intake during inter-dialytic periods can easily be assessed by measuring the changes in serum sodium concentration and in body weight.