Paracrine stimulation of vascular smooth muscle proliferation by diadenosine polyphosphates released from proximal tubule epithelial cells.

The purinergic receptor system plays an important role in the regulation of both vascular and tubular functions within the kidney; however, the release of purinergic agonists other than ATP by renal tissue is not known. In this investigation, we determine if kidney tissue is a source of diadenosine polyphosphates, which have high affinity for the P(2X) and P(2Y) receptors. Both diadenosine pentaphosphate and hexaphosphate were identified by matrix-assisted laser desorption ionization-mass spectrometry in extracts purified from both whole porcine kidney and from cloned cells of the LLC-PK1 cell line. Both polyphosphates in nanomolar concentrations were found to significantly stimulate the proliferation of vascular smooth muscle cells derived from rat thoracic aortas. The purinergic-receptor antagonist, suramin, did not significantly affect the growth-stimulatory properties of the polyphosphates. The growth stimulation of vascular smooth muscle cells by platelet-derived growth factor was potentiated by both diadenosine polyphosphates. We conclude that diadenosine polyphosphates are endogenous purinergic agonists of the kidney that have physiologic and pathophysiologic relevance. These epithelial cell metabolic products have vasoregulatory properties while linking the energy supply and tubular function.

HLA class I and class II antigens in Turkish patients with chronic ordinary urticaria.

BACKGROUND: Chronic urticaria is a common disease with an unclear pathogenesis, which may be resistant to therapy. Recent studies have focused primarily on a possible autoimmune basis. AIM. To investigate HLA class I and II antigens in a Turkish population with chronic ordinary urticaria (COU; not physical, vasculitic or contact), and identify susceptible HLA antigens. METHODS: HLA antigens were investigated in 55 patients diagnosed with COU, using a two-stage microdroplet lymphocytotoxicity test, with 104 healthy and genetically unrelated individuals evaluated as the control group. RESULTS: HLA Bw4 and HLA DQ1 antigens were significantly higher in the study group (odds ratio (OR) = 2.93, 95% CI 1.47-5.85, P = 0.003 and OR = 7.81, 95% CI 1.96-28.50, P = 0.001, respectively) whereas HLA-A24 antigen was higher in controls (OR = 0.36, 95% CI 0.15-0.86, P = 0.03). CONCLUSION: We propose that HLA-Bw4 and DQ1 antigens may be responsible for susceptibility to COU while HLA-A24 may have a protective role in the Turkish population.

Narrowband UVB phototherapy for small plaque parapsoriasis.

BACKGROUND: Narrowband UVB (NB-UVB) phototherapy has been shown to be effective for the treatment of various dermatoses. OBJECTIVE: To analyze the effects of NB-UVB phototherapy for small plaque parapsoriasis (SPP). METHODS: The response of 45 patients (24 females, 21 males, age range 20-58 years) with histologically confirmed SPP were assessed. NB-UVB therapy was given 3-4 times weekly. The initial treatment dose was 70% of the minimal erythema dose. The doses were increased gradually with a standard increment of 20/10/0. Clinical response was determined as follows: complete response (CR), at least 90% clearing of skin lesions; partial response (PR), at least 50% but less than 90% clearing and no response (NR), less than 50% clearing. The follow-up period was 6-24 months after the treatment. RESULTS: NB-UVB treatment led to CR in 33 of 45 patients (73.3%) with a mean cumulative dose of 14.3 J/cm(2) (range 3.2-24.1 J/cm(2)) after a mean number of 29 exposures (range 16-51 sessions); PR in 12 of 45 (26.6%) with a cumulative dose of 15.6 J/cm(2) (range 10.4-23.3 J/cm(2)) after a mean number of 29.4 exposures (range 25-50 sessions). Nineteen patients with CR had skin phototype II, 13 had type III and 1 had type I. Among the patients with PR, 7 had skin phototype II and 5 had type III. Postinflammatory hyperpigmentation was observed in 51% of the patients. Relapses occurred in six patients within a mean time of 7.5 months (2-12 months). CONCLUSION: NB-UVB phototherapy has several advantages over treatment with broadband UVB and PUVA. NB-UVB therapy for patients with SPP is an effective, safe and practical alternative treatment modality. Further larger studies with longer follow-up periods are necessary to determine the proper clinical response and long-term complications of NB-UVB therapy in this disease.

Audiological abnormalities in patients with vitiligo.

BACKGROUND: Accumulating evidence suggests that vitiligo is a systemic disease affecting the entire pigmentary system. AIM: To investigate the subclinical abnormalities of melanin-containing cellular elements of the auditory system in patients with vitiligo. METHODS: We studied the conventional audiometric investigations and brainstem auditory evoked responses (BAERs) of 57 active patients with vitiligo and 50 healthy human subjects. The I, III and V latencies, and I-III, III-V and I-V interpeak latencies (IPL) between the groups were compared. RESULTS: A mild degree of sensorineural hypoacusis was found in eight patients with vitiligo (14%), whereas no controls demonstrated abnormal audiological results (P =0.006). A statistically significant increase in both ears of the third peak latency (P =0.02, P = 0.01, respectively) and IPL I-III (P = 0.04, P = 0.008, respectively), and a significant increase of the fifth peak latency in the right ear (P = 0.04) were found, compared with controls, but no differences were found for other latencies and IPLs. CONCLUSIONS: Melanin may play a significant role in the establishment and/or maintenance of the structure and function of the auditory system and may modulate the transduction of the auditory stimuli by the inner ear.

Isolation and quantification of dinucleoside polyphosphates by using monolithic reversed phase chromatography columns.

In former studies, dinucleoside polyphosphates were quantified using ion-pair reversed-phase perfusion chromatography columns, which allows a detection limit in the micromolar range. The aim of this study was both to describe a chromatographic assay with an increased efficiency of the dinucleoside separation, which enables the reduction of analytical run times, and to establish a chromatographic assay using conditions, which allow MALDI-mass spectrometric analysis of the resulting fractions. We compared the performance of conventional silica reversed phase chromatography columns, a perfusion chromatography column and a monolithic reversed-phase C18 chromatography column. The effects of different ion-pair reagents, flow-rates and gradients on the separation of synthetic diadenosine polyphosphates as well as of diadenosine polyphosphates isolated from human platelets were analysed. Sensitivity and resolution of the monolithic reversed-phase chromatography column were both higher than that of the perfusion chromatography and the conventional reversed phase chromatography columns. Using a monolithic reversed-phase C18 chromatography column, diadenosine polyphosphates were separable baseline not only in the presence of tetrabutylammonium hydrogensulfate (TBA) but also in the presence of triethylammonium acetate (TEAA) as ion-pair reagent. The later reagent is useful because, in contrast to TBA, it is compatible with MALDI mass-spectrometric methods. This makes TEAA particularly suitable for identification of unknown nucleoside polyphosphates. Furthermore, because of the lower backpressure of monolithic reversed-phase chromatography columns, we were able to significantly increase the flow rate, decreasing the amount of time for the analysis close to 50%, especially using TBA as ion-pair reagent. In summary, monolithic reversed phase C18 columns markedly increase the sensitivity and resolution of dinucleoside polyphosphate analysis in a time-efficient manner compared to reversed-phase perfusion chromatography columns or conventional reversed-phase columns. Therefore, further dinucleoside polyphosphate analytic assays should be based on monolithic silica C18 columns instead of perfusion chromatography or conventional silica reversed phase chromatography columns. In conclusion, the use of monolithic silica C18 columns will lead to isolation and quantification of up to now unknown dinucleoside polyphosphates. These chromatography columns may facilitate further research on the biological roles of dinucleoside polyphosphates.