The active form of vitamin D, 1,25-dihydroxyvitamin D3, is a secosteroid hormone that binds to the vitamin D receptor (VDR), a member of the superfamily of nuclear receptors, and exerts a number of diverse biological functions. The natural hormone and synthetic VDR agonists are well known for their capacity to control calcium and bone metabolism, but they also regulate proliferation and differentiation of many cell types, and possess exquisite immunoregulatory properties, mostly by targeting dendritic cells (DC) and T cells. These properties have been clinically exploited in the treatment of different diseases, from secondary hyperparathyroidism to osteoporosis to psoriasis. The VDR is expressed by most cell types, including cells of the urogenital system such as prostate and bladder cells. In particular, the prostate has been recognized as a target organ of VDR agonists and represents an extra-renal synthesis site of 1,25-dihydroxyvitamin D3, but its capacity to respond to VDR agonists has, so far, been probed only for the treatment of prostate cancer. We have taken a different approach, and have analysed the capacity of VDR agonists to treat benign prostatic hyperplasia (BPH), a complex syndrome characterized by a static component related to prostate overgrowth, a dynamic component responsible for urinary irritative symptoms, and a possible inflammatory component. Pre-clinical data reviewed here demonstrate that VDR agonists, and notably BXL-628 (Elocalcitol), reduce the static component of BPH by inhibiting the activity of intra-prostatic growth factors downstream of the androgen receptor, and the dynamic component by targeting bladder cells. These data have led to a proof-of-concept clinical study that has successfully shown arrest of prostate growth in BPH patients treated with BXL-628. Ongoing clinical studies will assess the capacity of this VDR agonist to reduce symptoms and ameliorate flow parameters in BPH-affected individuals. The pronounced effects of BXL-628 on bladder smooth muscle cells and its anti-inflammatory properties indeed anticipate beneficial effects also on BPH-related lower urinary tract symptoms.

Androgens↗

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Endoluminal instillation of bisacodyl in patients with severe (slow transit type) constipation is useful to test residual colonic propulsive activity.

BACKGROUND: Chronic constipation is a frequent symptom among the general population, and a minority of cases do not respond to any therapeutic measures, except surgery. The purpose of this study was to test the residual colonic motor propulsive activity with a pharmacologic stimulus in a series of patients referred for severe constipation. PATIENTS: Twenty-five chronically constipated patients, slow transit type, age range 16-71 years, unresponsive to conventional medical treatment and referred for functional evaluation, entered the study. METHODS: Colonic manometry by means of an endoscopically positioned probe was carried out in all patients. Following a basal recording period, a placebo solution followed by 10 mg bisacodyl solution was infused into the colon through the more proximal recording port. RESULTS: After bisacodyl infusion, about 90% of patients showed a motor response characterized by the appearance (within on average 13 +/- 3 min) of one or more high-amplitude propagated contractions, the manometric equivalent of mass movements, and about 75% of these were followed (mean 18.5 +/- 4 min) by defecation. CONCLUSIONS: Physiological and pharmacological testing of colonic motor activity may be important in severely constipated patients, especially in those labeled as 'intractable', in whom more in depth investigation planning may encourage further therapeutic efforts.

Adult↗

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Rhabdomyosarcoma presenting as acute hematologic malignancy: case report and review of the literature.

The authors describe a case of undifferentiated rhabdomyosarcoma from unknown primary site, presenting as an acute hematologic malignancy with generalized lymphadenopathy, extensive bone marrow involvement and clinical and laboratory features of disseminated intravascular coagulation. Such a peculiar behaviour is known for rhabdomyosarcoma but is rare and can be a serious diagnostic problem for the clinician and the pathologist. The importance of a large spectrum immunohistochemistry as first diagnostic approach to any undifferentiated small-cell malignant tumor is stressed, together with the knowledge of the different immunoreactivity patterns. Desmin, MS-actin and myoglobin are the most reliable markers of this type of myogenic sarcoma.

Actins↗

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Castleman's disease: an unusual cause of mediastinal mass and anemia.

We reported a case of thoracic localized, mixed variant, Castleman's Disease (angiofollicular lymph node hyperplasia) with a favourable clinical course presenting with mediastinal mass, microcytic anemia, mild thrombocytosis, polyclonal hyper-gammaglobulinaemia and without symptoms. Castleman's Disease must be always considered in the differential diagnosis of solitary mediastinal masses. Transthoracic fine needle aspiration cytology is usually nondiagnostic; in fact, cytologically, Castleman's Disease can be confused with other mediastinal lymphoproliferative disorders (such as thymomas or lymphomas). The optimal therapeutic approach is unknown but a complete surgical resection is treatment of choice for localized disease.

Adult↗

PubMedDate not supplied

[Level of red blood cell phosphorilated compounds in nutritional anemias (author's transl)].

This paper deals with the determination of red blood cell phosphorilated compounds, by automated ion exchange chromatography, in clinically healthy subjects, in two patients with hypochomic iron deficiency anemia and in four patients with macrocytic folic acid deficiency anemia. In the cases of nutritional anemia examined significant variations in the level of glycolitic phosphorilated compounds have been observed. The total acid-soluble phosphate content presents a marked increase in patients with anemia, compared with clinically healthy subjects. Very high increase in the 2,3 DPG, F1, 6DP, R5P, G1, 6DP and IMP red blood cell content is observed. On the contrary, ATP red blood cell concentration presents a marked decrease in all the patients.

Adenosine Diphosphate↗

PubMedDate not supplied

[Atrial fibrillation and hyperthyroidism: results after thyroidectomy].

Hyperthyroidism patients can develop atrial fibrillation (AF) with a frequency range between 10 and 25%. The Authors consider 256 hyperthyroid patients operated in their Department, from 1985 to 2001. Before and after surgery, thyroid examination, routine blood tests and common diagnostic evaluations were performed. The follow-up has been 12 months and during this period a L-Thyroxine (50-200 mg/die) therapy has been arranged. Before surgery 59 patients (23%) showed an AF associated with palpitations (76%), asthenia (66%), tremors (54%) and dyspnea (43%). The onset of AF was less than 1 months in 18% of cases, less than 3 months in 30% and chronic in remaining 52%. The 87% of patients was already pharmacologically treated. All the patients were treated with anticoagulants, with a INR value between 2 and 3. After the surgery, 47% of patients presented a restoration of the sinusal rhythm, while the 53% showed a stronger therapeutic responsiveness to specific antiarrhythmic therapy. Treatment of FA hyperthyroid patients with FA tends to normalize the function of the thyroid gland (euthyroidism). In our experience the restoring of sinusal rhythm usually develops in patients with 50 years of age (45 +/- 5 years), while in older patients AF tends to be resistant to treatment.

Atrial Fibrillation↗

PubMedDate not supplied

Phosphatidyl inositol 4,5-bisphosphate-specific phospholipase C in bovine rod outer segment membranes.

Polyphosphoinositide-specific phosphodiesterase (phospholipase C) activity against phosphatidylinositol 4,5-bisphosphate has been examined in disrupted bovine retinal rod outer segments. The enzyme was strictly modulated by free calcium ion concentration and maximally activated at 10(-5) M Ca2+ (91 +/- 4 nmoles phosphatidylinositol 4,5-bisphosphate hydrolyzed/min/mg of protein). Guanine nucleotides did not affect in vitro phospholipase C activity either in the presence or absence of light, carbachol or epinephrine. The pH optimum at 10(-5) M Ca2+ in the presence of sodium deoxycholate was 6.5. The enzyme of bovine rod outer segments was concluded to be indirectly regulated by the phototransduction events.

Animals↗

PubMedDate not supplied

Resolution and characterization of two forms of phosphoinositide-specific phospholipase C from bovine rod outer segments.

Two forms (I and II) of phospholipase C, specific for phosphatidyl inositol 4,5-bisphosphate, were resolved from bovine retinal rod outer segment (ROS) cytosol by DEAE-Sepharose column chromatography. The two isozymes showed reproducible differences in their catalytic properties in spite of similar substrate specificity and hydrolyzed specifically inositol 4,5-bisphosphate in a Ca(2+)-dependent fashion. In the presence of deoxycholate (DOC), pH optima were at 6.5 and 7.0 for phospholipase C I and II, respectively. Maximal phosphatidylinositol 4,5-bisphosphate hydrolysis rates were obtained at 10(-4) and 10(-5)M Ca2+ for phospholipase C I and II, respectively. Treatment with cAMP-dependent protein kinase did not alter either isozyme activity. Further purification steps were prevented by the extreme lability of the isozymes.

Animals↗