HPLC in biopharmaceutical investigations of drugs representing pyrimidine derivatives (A review)

Pyrimidine derivatives are widely used for the treatment of viral diseases and cancer. The analysis of pyrimidine derivatives is typically performed using various chromatographic techniques, in particular, reversed-phase high performance liquid chromatography (HPLC). The separation is typically carried out with (7–30)-cm-long C₈ and C₁₈ silica gel columns, mainly at room temperature, and a 1–1.5 ml-min eluent flow rate. The column is eluted in an isocratic or gradient system, and a variety of mobile phases have been proposed. The detection is based on optical absorption or fluorescence measurements, or makes use of mass spectrometry. Various methods of extraction of pyrimidine derivatives from biological samples are discussed, and the corresponding detection limits are presented. __________ Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 41, No. 5, pp. 26–34, May, 2007.     

The characteristics of cardiomyopathy in different geographical regions]

Region-specific characteristics of hypertrophic cardiomyopathy (HC) and dilated cardiomyopathy (DC) were compared for 108 relevant patients living in Dubai (United Arab Emirates) and Moscow (Russia). Out of 49 citizens of Dubai 17 had HC, 32 DC, and 59 Moscow patients had HC in 23, DC in 36 cases. It was found that HC in Dubai tends to run a silent latent course, involving mainly basal septum and right ventricle. Apical lesions were more typical for Moscow citizens who also display more severe myocardial impairment. DC in Dubai produces weaker cardiac insufficiency and arrhythmia. Incidence of idiopathic and periportal DC proved higher in Dubai, while alcohol and virus infection underlie DC more frequently in Moscow.     

Effect of dietary protein on Masheri-induced drug metabolising enzymes

The modulation of drug metabolising enzymes by Masheri extract (ME) and Benzo(a)Pyrene [B(a)P] was studied in male Sprague Dawley rats fed different dietary protein levels. Two groups of 21 days old male Sprague Dawley rats were put on a high protein diet (SHP) with 20% Casein, and a low protein diet (SLP) with 3% Casein semisynthetic based diets for 12 weeks. The SLP fed animals showed lower basal levels of the Phase I activating enzymes viz. Cytochrome P450, Benzo(a)Pyrene hydroxylase, Benzphetamine demethylase and Phase II glutathione detoxification system viz. Glutathione (GSH) and Glutathione-S-transferase. ME and B(a)P treatment significantly depleted the glutathione detoxification system in the SLP group whereas an opposite effect was observed in the SHP group. Interstingly, ME and B(a)P treated rats in the SLP group showed a higher percent increase in the hepatic and pulmonary Phase I enzyme activities than those observed in the treated ME/B(a)P treated SHP rats. Furthermore, both ME and B(a)P significantly decreased the hepatic pool of vitamin A while a concomittant increase in that of vitamin C was observed.     

Hemodynamic effects of the treatment of hypertension with the calcium channel blocker diltiazem

The 1.5-benzotthazepine derivative diltiazem, which blocks slow calcium channels, is an effective hypotensive agent, used for the treatment of moderate hypertension. Treatment with diltiazem alone, its dose adjusted on an individual basis, controlled arterial blood pressure in 58% of the patients. With a 240 mg daily dose, blood pressure was controlled in 12 of 52 patients; when the daily dose was increased to 360 mg, blood pressure was controlled in another 18 patients. In the remaining 22 patients, blood pressure was only controlled after captopril was added in a daily dose of at least 50 mg. The drop of arterial blood pressure was associated with falling total peripheral resistance and end diastolic blood volume, and was accompanied by an increase in left-ventricular ejection fraction and myocardial oxygen want.     

Classical and anaplastic seminoma: difference in survival

Classical and anaplastic seminoma are traditionally treated with radiation therapy and are said to have the same prognosis. A retrospective study was undertaken of 90 seminoma patients treated with radiation therapy between 1961 and 1985. The classical group consisted of 71 patients of whom 50 had stage I and 21 had stage II disease. The anaplastic group consisted of 19 patients of whom ten had stage I and nine had stage II disease. The median follow-up time was 64 months for the entire group. The 10-year relapse-free survival rate for the classical group was 94% and for the anaplastic group was 70% (P less than .05). For patients with classical stage I disease, the relapse-free actuarial survival rate was 98%; for patients with anaplastic stage I disease, it was 64% (P less than .02). For the classical stage II disease group, the relapse-free actuarial survival rate was 84% and for the anaplastic stage II disease group, 75% (P less than .70). Four patients in the classical group (6%) had relapses; of these, one patient had local recurrence of tumor, and three had distant metastases. In the anaplastic group, four patients (21%) had relapses; two patients had local recurrence of tumor, and two had distant metastases. Therefore the data suggest a difference in survival and relapse rates between classical and anaplastic seminoma.     

Diagnostic and treatment problems in sarcoidosis in the therapist's practice

Altogether 231 sarcoidosis patients were observed. Chest x-ray showed stage I in 116 patients, stage II in 111 patients. Corticosteroid therapy was provided to stage II patients only, with signs of alveolitis activity, for which assessment lung scintigraphy with 67Ga, investigation of bronchoalveolar rinse and determination of the blood angiotensin converting enzyme should be performed. Various extrapulmonary manifestations like hepatosplenomegaly, skin rash, cardiac arrhythmia and conduction disorder, urinary syndrome, etc., were revealed in 28 patients. The authors discussed variants of a course of lesions of the internal organs in sarcoidosis, difficulties of their diagnosis, and indications for steroid therapy. They also recommend a further study of the extrathoracic manifestations of sarcoidosis which frequently determine prognosis of this disease (first of all, cardiac, renal and nervous system affections), serve indicators of its activity (erythema nodosum, uveitis, parotitis, etc.) and present considerable diagnostic difficulties.