Angiotensinogen promoter variants influence gene expression in human kidney and visceral adipose tissue.

Human angiotensinogen (AGT) gene promoter polymorphisms (G-217A; A-20C; G-6A) influence AGT transcription in vitro and have been implicated in the genetics of essential hypertension. We analysed the association among AGT promoter variants and AGT mRNA levels in human kidney and visceral adipose tissue (VAT) in vivo. Samples of kidney and VAT were obtained from 35 consecutive patients undergoing renal surgery. The AGT gene promoter of each patient was sequenced to identify variants. AGT gene expression was studied by real-time PCR TaqMan assay. Clinical data obtained before surgery were also considered in the statistical analysis. Two new polymorphisms at -175 and at -163 were identified. Although AGT expression was significantly higher in VAT than in the kidney, when both variants were present together AGT expression in VAT was about fivefold lower (P=0.033) than in the wild haplotype. This lower AGT expression in VAT suggests that the proximity and linkage of -175A and -163A variants might destabilize the binding of specific transcription factors to an acute-phase responsive element 3. Among the known AGT promoter variants, only -20C SNP has an important effect on tissue-specific differential AGT expression in the human tissues studied, inducing a 3.8-fold increase in AGT mRNA localized only in the kidney medulla (P=0.038). The other known polymorphisms (G-6A; G-217A) were not associated with different levels of AGT expression. Our results support the hypothesis that some human AGT promoter variants influence transcriptional activity in a tissue-specific way in humans.

Angiotensin II stimulates and atrial natriuretic peptide inhibits human visceral adipocyte growth.

OBJECTIVE: Cardiovascular peptides such as angiotensin II (Ang II) and atrial natriuretic peptide (ANP) have metabolic effects on adipose cells. These peptides might also regulate adipocyte proliferation and visceral adipose tissue (VAT) expansion. Well-differentiated and stabilized primary cultures of human visceral mature adipocytes (MA) and in vitro-differentiated preadipocytes (DPA) were used as a model to study regulation of VAT expansion. METHODS: Adipocyte differentiation was evaluated by Oil Red O staining and antiperilipin antibodies. MA and DPA from intra- and retro-peritoneal depots were treated with increasing Ang II (with or without valsartan, a highly selective, competitive, 'surmountable' AT1 antagonist devoid of peroxisome proliferator-activated receptor gamma agonistic activity) or ANP concentrations. Cell counts and bromodeoxyuridine incorporation were used to evaluate proliferation. Apoptosis was evaluated by Hoechst 33342 staining. 8-Bromo cyclic guanosine monophosphate (8Br-cGMP) was used to investigate ANP effects, and real-time PCR to evaluate Ang II and ANP receptors' expression. RESULTS: Cell proliferation was progressively stimulated by increasing Ang II concentrations (starting at 10-11 M) and inhibited by ANP (already at 10-13 M) in both MA and DPA. Co-incubation with increasing Ang II concentrations and valsartan indicated that Ang II effects were AT1-mediated. Indeed, AT2 receptors were not expressed. Valsartan alone slightly inhibited basal proliferation indicating an autocrine/paracrine growth factor-like effect of endogenous, adipocyte-derived Ang II. 8Br-cGMP experiments indicated that the effects of ANP were mediated by the guanylyl cyclase type A receptor. CONCLUSION: A cell-culture model to study VAT growth showed stimulation by Ang II and inhibition by ANP at physiological concentrations. Because similar effects are likely to occur in vivo, Ang II and ANP might be important modulators of VAT expansion and associated metabolic and cardiovascular consequences.

Urinary Tamm-Horsfall protein increased after potassium citrate therapy in calcium stone formers.

OBJECTIVES: To evaluate the effect of oral potassium citrate therapy on urinary excretion rates of citrate. Tamm-Horsfall protein (THP), and on calcium oxalate monohydrate crystal agglomeration inhibition [tm], in patients with recurrent calcium stone formation. METHODS: To evaluate the effect of oral therapy with potassium citrate on urinary citrate, THP, and [tm], 24-hour urine samples were collected before and at least 2 months after initiation of oral potassium citrate therapy in 33 calcium stone-forming patients who had no dietary restrictions. The citrate concentration was measured by an adaptation of a citrate lyase method. Urinary disaggregated THP concentration was determined with a quantitative enzyme-linked immunosorbent assay. The [tm] was determined by observing the effects of patients' urine, before and after oral potassium citrate therapy, on the uptake of 45Ca2+ onto the surfaces of added preformed calcium oxalate crystals in a supersaturated solution of calcium oxalate, using the in vitro kinetic method described by other investigators. RESULTS: We observed an increased urinary excretion rate of citrate from a mean of 1.9 mmol/24 h prealkali to 2.6 mmol/24 h postalkali (P < 0.0004) and of THP from a mean of 94.0 mg/24 h prealkali to 199.3 mg/24 h postalkali (P < 0.0016). A corresponding increase in [tm] from a mean of 177.1 minutes prealkali to 221.0 minutes postalkali (P < 0.024) was also observed. CONCLUSIONS: To our knowledge this is the first report correlating increased urinary citrate with THP excretion rate following oral alkalinization with potassium citrate in calcium stone formers. Of clinical importance is the corresponding increase in [tm], which was previously shown to be inversely related to stone-forming activity. Moreover, urinary citrate and THP are known to have a synergistic effect on [tm]. Our data suggest that the effectiveness of potassium citrate therapy in calcium stone-forming patients may, at least in part, be due to increased levels of THP.

Systemic sclerosis following anti-androgenic treatment for prostatic adenocarcinoma.

We describe a male patient who developed systemic sclerosis following orchiectomy, radiotherapy and anti-androgenic treatment for prostatic adenocarcinoma. This case appears interesting as it further supports the possibility of a relationship between neoplasia and systemic sclerosis. The concurrence of scleroderma and iatrogenic hypoandrogenism suggests that hormonal influences may also play a role in the pathogenesis of this connective tissue disorder.

[Ketoprofen efficacy and tolerance in simple painful shoulder]. / Efficacia e tollerabilità del ketoprofene nella spalla dolorosa semplice.

Thirty patients presenting with painful shoulder syndrome were treated with i.m. ketoprofen 100 mg b.d. for 8 days to assess the efficacy and tolerance of the above treatment regime. The patients' condition was monitored by clinical, instrumental and laboratory examinations. Ketoprofen was found to be significantly effective in all cases of non calcific rotator cuff tendinitis while no improvement was noted in calcific tendinitis. The above data confirm the efficacy and tolerance of ketoprofen in the treatment of painful shoulder syndrome as an alternative to local steroid therapy.

Histopathological study of iron deposit distribution in the rheumatoid synovium.

A qualitative and semi-quantitative evaluation of synovial iron deposits in 20 patients with rheumatoid arthritis (RA) and in 12 patients presenting with degenerative and traumatic joint disease was carried out. Ferric iron deposits, abundant and preferentially distributed in the superficial and deeper connective tissue layers in the RA patients, were more limited and prevalently sited in the synovial lining layer in the controls. These results further underline the increase in synovial iron stores found in active RA and the role played by iron deposits in sustaining inflammation, as has been reported in the literature.

[Telethermography in the early diagnosis and clinico-therapeutic monitoring of Sudeck's disease]. / La teletermografia nella diagnosi precoce e nel monitoraggio clinico-terapeutico della malattia di Sudeck.

In order to evaluate the potential value of telethermography in the early diagnosis of Sudeck's disease, the authors examined 10 patients presenting with this condition. Mean disease duration was 3.2 months and algodystrophic lesions in all patients were localized in one of the lower extremities. Ten healthy subjects, with mean age and sex distribution similar to those of the patients with Sudeck, were chosen as controls. Clinical examination, laboratory tests and telethermography were performed every two weeks for three months; X-rays of the affected limbs were also performed at the beginning and at the end of the study. All patients with algodystrophy were treated with salmon calcitonin (100 U.I./die/i.m. during the first 2 months and 100 U.I. on alternate days during the last month). Clinical-therapeutic thermographic monitoring showed that the localized hyperthermic pattern, initially shown in all patients (temperature levels at least three centigrades above normal values), later underwent a progressive time-related reduction leading to normalization. These results enable the authors to confirm the potential value of telethermography in the early diagnosis of Sudeck's disease and in its clinical monitoring, particularly in relation to therapy.