Enantioselective reduction of pentoxifylline to lisofylline using whole-cell Lactobacillus kefiri biotransformation.

Lisofylline (LSF) is a drug candidate that has been under investigation for acute respiratory distress syndrome, acute lung injury, septic shock and mucositis. As LSF is not commercially available in our country, we produced it for pharmacokinetic studies. In the present work whole-cell reduction of pentoxifylline [1-(5-oxohexyl)-3,5-dimethylxanthine] to LSF [1-(5R-hydroxyhexyl)-3,5-dimethylxanthine] using Lactobacillus kefiri DSM 20587 was investigated. Glucose or 2-propanol was used as a co-substrate to regenerate the NADPH cofactor. The reaction conditions were optimized. The influence of different concentrations of co-substrates on the yield and enantioselectivity of the biotransformation of pentoxifylline into LSF were tested. Maximum yield (100%) of biotransformation was reached in the presence of glucose as a co-substrate. At glucose concentrations of 675 and 900 mM the bioreduction of pentoxifylline proceeded highly enantioselectively (enantiomeric excess for the R enantiomer of 98%).

Determination of phenothiazine derivatives by high performance thin-layer chromatography combined with densitometry.

A high performance thin-layer chromatography (HPTLC) method combined with densitometry for determination of phenothiazine derivatives is described. Quantitation was performed in reflectance mode by using a computer-controlled densitometer Desaga CD 60. Established calibration curve (r > 0.999), precision (RDS values: 0.95-2.53%), detection limits as well as recovery values (101.1-102.8%) were found to be satisfactory. The presented method is rapid, precise and sensitive, and may be alternative to traditionally used HPLC. The method has been successfully applied in the analysis of pharmaceutical formulations.

Biotransformation of praziquantel by human cytochrome p450 3A4 (CYP 3A4).

Praziquantel (PZQ) is the drug of choice for the treatment of human schistosomiasis. It is estimated that about 200 million people in the world are currently affected by this tropical disease. Now PZQ is also used in malaria treatment. The usefulness of PZQ as antimalarial drug is important because of rapid development of resistance to usually applied drugs. PZQ undergoes extensive metabolism in human body, mainly in liver by two cytochrome P-450 isoenzymes 2B1 and 3A. As the result of these biotransformations numerous mono- and dihydroxylated derivatives in B, C and D ring are formed. Two metabolites have been fully identified and described, as cis- and trans-4-hydroxypraziquantel. Up to now there were created many different in vitro and in vivo models of PZQ biotransformations. In vitro model of PZQ biotransformation was created by using human cytochrome P-450 3A4 expressed in Eschelichia coli and Saccharomyces cerevisiae. In the first experiment we have used human cytochrome P-450 3A4 from Escherichia coli (isolated on NTA-column). In the second experiment microsomes isolated from Saccharomyces cerevisiae containing coexpressed human CYP 3A4, human CYP-reductase and human cytochrome b5 were used. The reactions were monitored by HPLC and MS.

[Systemic diseases in patients with central retinal artery occlusion or its branches in the material of Department of Ophthalmology of Medical University of Lublin]. / Schorzenia ogólnoustrojowe u pacjentów z zamknieciem tetnicy srodkowej siatkówki lub jej galezi w materiale Kliniki Okulistyki Akademii Medycznej w Lublinie.

Patients with central retinal artery occlusion usually suffer from serious systemic diseases that could be potentially threatening life. Retinal emboli are associated with the presence of hypertension and other cardiovascular diseases, diabetes mellitus, hematological disturbances or infections. The goal of this study is the assessment of the most common coexisting systemic diseases in patients with the occlusion of retinal arteries. We retrospectively studied 51 patients with symptomatic retinal artery occlusion treated in The Department of Ophthalmology, Medical University of Lublin from 1990 to 2003. The most common concomitant diseases were hypertension, cardiovascular diseases and brain stroke. Eight of 51 patients died. The most frequent reason of death was cerebral stroke. Cardiovascular and cerebovascular examinations should be recommended for patients with retinal emboli.

[Bee sting of the cornea--a case report]. / Uzadlenie rogówki przez pszczole--opis przypadku.

Published reports on bee stings of the cornea are rare, especially when it occurs in the winter season. have the potential for causing serious ophthalmologic problems. The venom in the sting can produce toxic and immunologic reactions. The result is acute ocular inflammation, which is usually confined to the anterior segment of the eye. The aim of our work is to present a 84-year-old man who was stung by a bee on the left cornea, while taking care of a swarm of bees. The main symptoms were pain, oedema of eyelids, conjunctival injection, keratitis and iritis. The sing was present in the cornea. After the removal of retained stinger and pharmacological treatment we observed rapid improvement.

[Value of conjunctival biopsy in the diagnosis of sarcoidosis]. / Przydatnosc biopsji spojówki w diagnostyce sarkoidozy.

The eye signs of sarcoidosis may be observed in patients with no evidence of any other symptoms. In this paper a patient with diagnosis of sarcoidosis was presented. The proper diagnosis and treatment were possible after results of conjunctival biopsy. Conjunctival biopsy could be a useful method in the diagnosis of many systemic diseases, including sarcoidosis.

[Central serous choroidopathy in a 57 years old woman]. / Choroidopatia centralna surowicza u 57-letniej chorej.

A 57 years old patient with unilateral decrease of vision with accompanying micropsia and metamorphopsia is presented. After ophthalmological examination, fluorescein angiography and ultrasound examination we diagnosed idiopathic central serous choroidopathy. After photocoagulation the improvement of visual acuity was achieved.

The research on biotransformation of praziquantel.

Praziquantel (PZQ), a broad spectrum antihelmintic drug, is extensively metabolized in the liver, yielding mainly monohydroxylated and dihydroxylated phase-I-metabolites. However, the exact chemical structures of the most metabolites are still unknown. In the presented research, three types of PZQ biotransformations were performed: biotransformation with the whole cells of Saccharomyces cerevisiae, with cytochrome c from Saccharomyces cerevisiae and with microsomes isolated from Saccharomyces cerevisiae. To describe the obtained metabolites TLC, RP-TLC, and HPLC were used.

[Central retinal occlusion in the course of idiopathic carotid-cavernous fistula]. / Zamkniecie zyly srodkowej siatkówki w przebiegu samoistnej przetoki szyjno-jamistej.

PURPOSE: This study presents the case history of a 58-year-old woman with a diagnosed spontaneous carotid-cavernous fistula on the left side and mild hypertension. THE FIRST SIGNS OF THIS DISEASE WERE: Headache, double vision, proptosis, ptosis of the left upper lid, paresis of the left abducens nerve, conjunctival edema, dilatation and tortuosity of the vessels in conjunctiva and episclera. In the course of this disease a massive central retinal vein occlusion occurred in the left eye. The angiography demonstrated carotid-cavernous fistula on the left side with pathological blood flow. Embolization of the fistula was attempted, but it was not successful. During 6 months of follow up, the signs of central retinal vein occlusion and other manifestations disappeared. CONCLUSIONS: A spontaneous carotid-cavernous fistula should be considered as one of the contributing factors of the central retinal vein occlusion, particularly in menopausal women with concomitant arterial hypertension. The significant reduction of neurological and ophthalmological symptoms and signs may suggest, that arteriovenous shunt is closed.

[Evaluations of ophthalmological care expectation in the opinion of countryside dwellers in the example of the Wola Uhruska region]. / Ocena potrzeb zdrowotnych w zakresie narzadu wzroku i ich realizacji w opinii mieszkanców terenów wiejskich na przykladzie gminy Wola Uhruska.

PURPOSE: The aim of the study was the evaluations of ophthalmological care expectation in opinion of countryside inhabitants and their knowledge of eye diseases. MATERIALS AND METHODS: The analysis was performed based on the results of a survey, which covered 198 rural inhabitants living in Wola Uhruska region. The study was carried out during training arranged by Medical University of Lublin in July 2002. RESULTS: The obtained material was analysed and presented in the form of diagrams and written report. The results of the study showed, that 77% of patients was dissatisfied with the ophthalmologic health care access, despite, that the nearest ophthalmologic practice was in the distance of 30 km. Unfortunately, only 25% of persons could indicate the cause of their eye problems. It is important, to provide more information of eye condition for all patients.

TH1/TH2 balance in the subretinal fluid of patients with rhegmatogenous retinal detachment.

BACKGROUND: The pathogenesis of rhegmatogenous retinal detachments remains unclear, but some data suggest immune system involvement. Cytokines are substances secreted by cells in order to modulate the function of other cells. They exert primarily local effects. Because the TH1/TH2 balance is crucial in the immune response, the predominance of one cytokine profile in subretinal fluid may be of particular importance in understanding its pathogenesis. MATERIAL/METHODS: We measured the titres of IL-10 and tIL-12 in the subretinal fluid of 36 rhegmatogenous retinal detachment patients using ELISA assays. RESULTS: The mean level of IL-10 and tIL-12 in the subretinal fluid was 4.75 pg/ml and 106.5 pg/ml, respectively. CONCLUSIONS: It would appear that IL-10 and IL-12 are produced by cells in subretinal fluid, and their presence may be evidence for an existing inflammatory process. Despite the tendency to decreased cytokine concentration over time and the tendency to higher concentrations of IL-10 and tIL-12 when the detachment of the retina is more extensive, no predominance of TH1- or TH2-type response was observed.

The occurrence of primary open angle glaucoma in a family.

The occurrence of primary open glaucoma (POAG) in families proves the hypothesis that POAG is a disease with underlying genetic factors. This work describes a family of four generations, in which eight members suffered from POAG. In the 3rd and 4th generation members, the disease occurred at an early age (between the age of 20-40 years), i.e. at a much earlier age than it could be expected. Therefore, a need arises to keenly observe families in which POAG is present.

The level of alpha-antitrypsin and ceruloplasmin in the subretinal fluid of patients with rhegmatogenous retinal detachment.

UNLABELLED: The aim of the study was to determine alpha-antitrypsin (AAT) and ceruloplasmin (CER) level in the subretinal fluid of patients with rhegmatogenous retinal detachment (RRD). Investigation was performed in 41 patients (22 women, 19 men) operated on for RRD at the age from 24 to 81. The group of patients was divided with regard to the extent and duration of RRD. In 24 patients detachment involved 1 or 2 quadrants and in 17 patients--3 or 4 quadrants. In 16 subjects RRD lasted shorter than 2 weeks, in 6 patients--about one month and in 19 patients--from 1 to 3 months. The subretinal fluid was collected during operation. The levels of the examined substances were determined with the radial diffusion method on Nor-Partigen plates by Behring. The results were as follows: mean AAT concentration in the subretinal fluid of all the patients operated on for RRD was 0.739 +/- 0.475 g/l and CER was 0.186 +/- 0.122 g/l. Mean AAT concentrations did not differ statistically significantly between the group with bigger and smaller retinal detachments while CER level was higher in the group with a bigger RRD. Mean AAT and the CER concentration was statistically significantly higher in the group with RRD lasting from 1 to 3 months compared with the group with RRD lasting shorter than one month. CONCLUSIONS: the fact of finding acute phase proteins in subretinal fluid suggests that they may play a part in the pathogenesis of RRD by affecting the intensity of local inflammatory reaction.

The level of total sialic acid, alfa-antitrypsin, ceruloplasmin in the serum of patients with choroidal melanoma.

Melanoma of the choroid is a fatal disease because of its metastases. The quest is ongoing for more reliable serum markers for detecting and staging ocular melanoma. Total serum sialic acid and acute phase proteins are valuable adjuncts in the management of malignancies, including melanoma. The aim of the paper was to asses the level of total sialic acid (TSA), total sialic acid to total protein (TP) ratio (TSA/TP) and the level of alfa-antitrypsin (AAT) and ceruloplasmin (CER) in patients with choroidal melanoma. The concentrations of TSA, TP, AAT and CER were evaluated in 61 patients with choroidal melanoma and 84 healthy controls. 36 patients had larger tumors and 25 patients had smaller melanomas. 36 patients were treated with brachytherapy. The mean concentration of TSA in all intraocular melanoma patients was 84.86 +/- 19.37 mg/dl and was significantly higher than in control group 53.63 +/- 8.47 mg/dl (p < 0.001). TSA level was significantly higher in patients with large tumors than in those with smaller choroidal melanomas. There were not differences between groups of patients treated with brachy-therapy and those not treated. TSA/TP in melanoma patients was 11.88 +/- 2.97 and it was higher than in control group 7.32 +/- 1.21 (p < 0.001). AAT level was 236.56 +/- 141.53 mg/dl in the group of melanoma patients and in the control group was 226.42 +/- 46.74 mg/dl but the differences were not statistically significant. The concentration of CER in the study group was 28.25 +/- 11.01 mg/dl and in the control group it was 29.56 + 6.33 mg/dl but the differences were not statistically significant. The assessment of TSA in blood serum may be useful in evaluation of patients with choroidal melanoma.