Determination of some psychotropic drugs in serum and saliva samples by HPLC-DAD and HPLC MS.

A simple, rapid and sensitive HPLC-DAD method has been developed and validated for the simultaneous determination of seven psychotropic drugs (risperidone, citalopram, clozapine,quetiapine, levomepromazine, perazine and aripiprazole) in human serum or saliva samples. The chromatographic analyses were performed on a XSELECT CSH Phenyl-Hexyl column with a mobile phase containing methanol, acetate buffer at pH 3.5 and 0.025mL(-1) diethylamine. The influence of concentration of methanol in injection samples and injection volume on peak symmetry and system efficiency was examined.The full separation of all investigated drugs, good peaks' symmetry and simultaneously high systems efficiency were obtained in applied chromatographic system. The method is suitable for the analysis of investigated drugs in human plasma or saliva for psychiatric patients for control of pharmacotherapy, particularly in combination therapy. HPLC-MS was applied for verification of the presence of drugs and their metabolites in serum and saliva samples from patients.

Serum Th1 and Th2 profile cytokine level changes in patients with Graves' ophthalmopathy treated with corticosteroids.

The aim of this study was to estimate the influence of corticosteroids on Th1 and Th2 serum cytokine balance in patients with GO: IFNgamma, TNFalpha, IL-4 and IL-10. Further, we tested the hypothesis of an up-regulation of Th2 immune response during successful treatment with corticosteroids to explain their beneficial effect in Graves' ophthalmopathy. Serum cytokines were detected in three groups of subjects: 20 patients with Graves' disease without ophthalmopathy (Gd), 16 patients with clinical symptoms of ophthalmopathy (GO) (CAS over 3 points, last consultation record for GO less than a year old) and 16 healthy volunteers. Corticosteroid therapy consisted of intravenous infusions of methylprednisolone (MP) (2 series, 3 g each time) and subsequent treatment with oral prednisone (60 mg per day) in a tapering schedule. The serum samples were collected 24 hours before MP, 24 hours after MP, 14 days of treatment with prednisone and at the end of corticosteroid therapy. The levels of IFNgamma, TNFalpha, IL-4 and IL-10 in the serum were determined using ELISA. Statistical significance was estimated by the Mann-Whitney U-test. Our findings show a deviation to systemic Th2 profile cytokines in Graves' disease. In patients with GO, we found a significantly increased serum IL-10 concentration. In corticosteroid-responsive patients, the balance of serum cytokines IL-4/IFNgamma, IL-4/TNFalpha, IL-10/IFNgamma and IL-10/TNFalpha increased and remained upregulated until the end of the study. In non-responders, the balance of serum cytokines studied increased after methylprednisolone but declined markedly during continuation of the therapy with prednisone. In summary, our results show that efficient corticosteroid therapy may be related to its influence on Th2/Th1 profile cytokine balance. The upregulation of serum IL-4 and IL-10 during successful treatment with corticosteroids indicate the possibility of using these cytokines as predictors of the beneficial effect of corticosteroids in Graves' ophthalmopathy.

Serum L-selectin and ICAM-1 in patients with Graves' ophthalmopathy during treatment with corticosteroids.

UNLABELLED: Circulating forms of L-selectin were found to be elevated in several autoimmune diseases. ICAM-1 has been suggested a predictor of the onset of GO. The aim of the study was an estimation of serum L-selectin and ICAM-1 in patients with Graves' disease with ophthalmopathy during treatment with corticosteroids to assess their potential as a guideline of immunosuppressive therapy. We detected serum L-selectin and ICAM-1 in three groups of subjects: 20 patients with Graves' disease without ophthalmopathy (Gd), 17 patients with clinical symptoms of ophthalmopathy (CAS> or =3, anamnesis of GO> or =1 year) and 24 healthy volunteers. Corticosteroid therapy consisted of intravenous infusions of methyloprednisolone (MP) and subsequent treatment with oral prednisone (P). The serum samples were collected 24 h before MP, 24 h after MP, 12+/-2 days of treatment with prednisone and after the end of the corticosteroid therapy. The levels of soluble L-selectin and ICAM-1 in the serum were determined by the ELISA method. The statistical significance was estimated by the Mann-Whitney U-test. Serum L-selectin and ICAM-1 were significantly increased in patients with GO (respectively 1182+/-222 and 438+/-68 ng/ml) and in patients with Graves' disease without ophthalmopathy (respectively: 1168+/-130 and 343+/-109) in relation to the controls. After MP treatment in corticosteroid-responsive patients (improvement in CAS < or =1) serum concentration of L-selectin and ICAM-1 decreased significantly and gradually increased during subsequent treatment with prednisone. In corticosteroid-responsive patients serum L-selectin was significantly higher before MP administration and after P treatment in relation to corticosteroid-resistant subjects. CONCLUSIONS: 1. Serum L-selectin and ICAM-1 were elevated in patients with active GO 2. Methyloprednisolone decreased levels of the studied adhesion molecules in corticosteroid-responsive patients with GO 3. Lack of clinical results in corticosteroid therapy in patients with a low starting L-selectin level would suggest the possibility of serum L-selectin estimation as a prognostic for immunotherapy efficacy.

[Pregnancy complicated by type I, type II and gestational diabetes: experiences from the diabetic-obstetric center of Bialystock]. / Ciaza powiklana cukrzyca typu 1, typu 2 oraz cukrzyca ciezarnych w materiale Bialostockiego Osrodka Diabetologiczno-Polozniczego.

The aim of the study was the analysis of pregnancy outcome, newborn status, metabolic control and obstetric failure in 365 pregnant diabetic patients treated in Bialystok Diabetic-Obstetric Center. Abortions occurred in 1.64% of pregnancies, intrauterine deaths--in 1.1%, and newborns deaths--in 2.47% cases. Macrosomia was observed in 14.8% of children (from 12% in type 1--up to 25% in gestational diabetes class G2). Congenital malformations were seen in 16 newborns of type 1 diabetic women (9.6%), 2 newborns of type 2 diabetics (22.2%), 6 children of mothers with gestational diabetes class G1 (4.2%) and 4 (8.3%)--class G2. The discussion underlines the role of a long duration of the disease as a key factor increasing the risk of complications and the importance of a good metabolic control before and shortly after conception.

A pilot study of the effect of the glycosaminoglycan sulodexide on microalbuminuria in type I diabetic patients.

Fifteen out-patients with type I diabetes mellitus and microalbuminuria (mean +/- SEM: 95.4 +/- 13.9 micrograms/min), were administered the glycosaminoglycan sulodexide, with the aim of investigating its influence on the rate of albumin excretion. Sulodexide was given intramuscularly in a dose of 600 lipoproteinlipase releasing units/day for three weeks. Albumin excretion was measured before dosing, at weekly intervals during dosing and also during the subsequent follow-up period of six weeks. Sulodexide yielded a clear-cut and statistically significant lowering of albumin excretion after the first week of treatment (from 95.4 +/- 13.9 micrograms/min to 53.6 +/- 11.1 micrograms/min; p = 0.0055); albumin excretion was further decreased after three weeks of treatment (26.5 +/- 6.05 micrograms/min; p = 0.0007) and was maintained during the follow-up period, at the end of which the mean value was still significantly lower than at baseline (39.6 +/- 10.3 micrograms/min; p = 0.01). Sulodexide short-term administration did not influence the routine haematological, haematochemical and coagulative tests performed contemporaneously. Patients' compliance with treatment was very good and no adverse events were reported.

Effect of glycosaminoglycans on urinary albumin excretion in insulin-dependent diabetic patients with micro- or macroalbuminuria.

The aim of this study was to investigate whether sulodexide treatment is capable of influencing urinary albumin excretion rate (UAER) in insulin-dependent diabetes mellitus patients (type I) with micro- or macroalbuminuria. A total of 14-inpatients (seven with micro and seven with macroalbuminuria) were enrolled and were treated first intramuscularly with a 60 mg vial of sulodexide/day for 10 days, and then orally with 25 mg capsules twice a day for 21 days. UAER was estimated before starting treatment (T0), after the i.m. treatment phase (T1) and at the end of the oral treatment (T2). No statistically significant differences in hematochemical and coagulative parameters were registered after treatment, with respect to basal values. On the contrary, a marked decrease in UAER mean values was registered at the end of both the parenteral and the oral treatment periods (T0: 349.9 mg/24 h, range 80-820; T1: 237 mg/24 h, range 7-620; T2: 91.4 mg/24 h, range: 2-306). All the differences were statistically significant (P < 0.001) versus baseline. At T2, a normalisation of UAER was observed in three microalbuminuric and in two macroalbuminuric patients, and a remarkable decrease was found in additional four and five patients, respectively. UAER was found to be still significantly lower than at baseline after 6 weeks of follow-up. This preliminary study suggests that sulodexide is effective in reducing UAER in type I patients with diabetic nephropathy.

[Idiopathic Fanconi syndrome in an adult]. / Samoistna postac zespolu Fanconiego u osoby doroslej.

Fanconi syndrome is a complex destruction of proximal renal tubuli which leads to glycosuria, aminoaciduria, phosphaturia and uraemia. These disturbances are accompanied with hypophosphatemia, osteomalacia and frequently hypokalemia. A 32-yrs. old woman diagnosed as suffering for 10 yrs. with Fanconi syndrome was admitted to the clinic with pain and numbness of the right leg which made walking difficult this resulted from progressive bone destruction. Biochemical disturbances and osteomalacia which are typical for Fanconi syndrome was confirmed in 1984. The reason for 3 hospitalizations in 1990-1992 were similar--especially leg pain and symptoms of uraemia. Recent X-rays showed osteomalacia with osteoporosis and progressive bone destruction. After she was put on a uremic diet, given vitamin D, calcium, phosphorus and sodium bicarbonate, there was a significant decrease in leg pain and relatively normal biochemical parameters.

[A case of non-Hodgkin's lymphoma of the thyroid gland]. / Przypadek nieziarniczego chloniaka tarczycy.

A case is reported of centrocytic-centroblastic malignant lymphoma situated in the thyroid and simulating goitre. Attention is called to difficulties in establishing of correct diagnosis.