Composition and cardioprotective effects of Primula veris L. solid herbal extract in experimental chronic heart failure.

BACKGROUND: High interest in chronic heart failure (CHF) is accounted for by its high incidence, poor prognosis, growing number of hospital admissions due to the heart failure relapse, and inadequate treatment. These facts necessitate a search for new pharmacological agents for the CHF correction. Herbal medicinal products appear to be very promising as they have a noticeable therapeutic effect and tend to be more harmless in comparison to the most of synthesized medications. PURPOSE: Our aim was to study the composition of the Primula veris L. solid herbal extract (PVSHE) and its effects on the myocardial contractile function in animals with experimental CHF. STUDY DESIGN: The study design involved the identification of the raw material composition of the P. veris L. extract. For the experimental part of our research, we used the model of CHF to elucidate the cardioprotective properties of PVSHE. METHODS: The active extract constituents were isolated by thin-layer chromatography and column chromatography; the extract components were identified by high-performance liquid chromatography, ultraviolet spectroscopy (UVS), and nuclear magnetic resonance spectroscopy (NMRS). To model CHF, L-isoproterenol at a dose of 2.5 mg/kg was intraperitoneally injected to the experimental rats twice a day for 21 days. Cardiac output was assessed with the loading test, adrenoreactivity test, and maximum isometric loading test; CHF markers adrenomedullin and copeptin were detected in blood plasma with ELISA kit for adrenomedullin and copeptin (Coud-Clone Corp., USA). RESULTS: P. veris L. solid herbal extract contains flavonoid aglycons (apigenin, quercetine, kaemferol), flavonoid glycosides (cinarozid, rutin, hyperozid), as well as polymethoxylated flavonoids acting as chemotaxonomic markers for the genus Primula (8-methoxy-flavone; 3',4'methylenedioxy-5'-methoxyflavone). The substance 3',4'methylenedioxy-5'-methoxyflavone has been isolated from the primrose herb for the first time. We showed that the PVSHE has a cardioprotective effect when it was administered at a dose of 30 mg/kg in the experimental CHF, as evidenced by a lower number of animal death, lower level of CHF markers in the blood plasma of the experimental animals, the higher increase in rate of myocardial contraction and relaxation, the higher level of left ventricular pressure (LVP) and of maximum intensity of structural performance (MISP), as compared to the control group. CONCLUSION: P. veris L. solid herbal extract contains flavonoid aglycons, flavonoid glycosides, and polymethoxylated flavonoids. The herbal agent increases the myocardial contractility in experimental CHF.

[Influence of the dense extract from herb of Primula veris L. On the oxidative stress development and the functional state of the cardiomyocytes mitochondria of rats with experimental chronic heart failure]. / Vliianie gustogo ékstrakta iz travy pervotsveta vesennego na razvitie oksidativnogo stressa i funktsional'noe sostoianie mitokhondrii kardiomiotsitov krys s éksperimental'noi khronicheskoi serdechnoi nedostatochnost'iu.

Experimental chronic heart failure (CHF), caused by administration of L-isoproterenol (2.5 mg/kg twice a day intraperitoneally for 21 days), promotes uncoupling of respiration and oxidative phosphorylation. The rate of mitochondrial oxygen consumption in the metabolic state V3 by Chance in animals with CHF decreased by 53.3% (p<0.05) with malate using (as an oxidation substrate feeding сomplex I of the electron transport chain (ETC)), by 70.6% (p<0.05) with succinate using (сomplex II substrate) and by 63.6% (p<0.05) when malate and succinate were added simultaneously. The respiratory control ratio significantly decreased 2.3 times for сomplex I, 2.5 for сomplex II, and 2.6 times for the simultaneous operation of two respiratory chain complexes in mitochondria of CHF rats compared to intact animals. Mitochondrial dysfunction in experimental CHF is evidently due to the development of oxidative stress. It was revealed that the content of malonic dialdehyde (MDA) in the group of rats with experimental CHF was higher by 54.7% (p<0.05), as compared with intact animals. The activity of superoxide dismutase (SOD) and catalase was lower by 17.5% (p<0.05), and by 18.4%, respectively than in the intact group. The dense extract from herba of Primula veris L. (DEHPV) 30 mg/kg limits the development of mitochondrial dysfunction in rats with experimental CHF, as evidenced by an increase in the role of V3 respiration for the first and second respiratory chain complexes in 1.7 (p<0.05) and 2.0 times (p<0.05), respectively, the ratio of respiratory control (RCR) - 1.7 times (p<0.05) for сomplex I and 2 times (p<0.05) for сomplex II compared with the negative control. The concentration of MDA was by 15.7% (p<0.05), lower and the activity of SOD was by 56.3% (p<0.05) higher.

[Levodopa-carbidopa intestinal gel in the treatment of patients with Parkinson disease: results of a 12-month open study]. / Levodopa-karbidopa intestinal'nyi gel' v terapii bol'nykh s razvernutymi stadiyami bolezni Parkinsona: rezul'taty 12-mesyachnogo otkrytogo issledovaniya.

AIM: To evaluate the long-term safety and efficacy of intrajejunal levodopa-carbidopa intestinal gel (LCIG) infusion in the treatment of patients with severe stages of Parkinson disease (PD) who did not respond adequately to treatment with oral drugs. MATERIAL AND METHODS: A large-scale international prospective open-label 54-week study of LCIG in patients with PD with severe motor fluctuations was carried out. A total of 48 patients were enrolled in Russia, 46 patients (95.8%) had PEG-J inserted, and 43 of them completed the study. The safety, including adverse events (AEs), infusion system and pump failures analysis, number of patients completely terminated the study, and efficacy (duration of "off" periods, "on" periods with or without troublesome dyskinesias, UPDRS scores, Clinical Global Impression, Quality of Life (PDQ-39, EQ-5D и EQ-VAS) dynamics, an analysis of patient's diaries) were assessed throughout the whole study. RESULTS: The majority of AEs were mild or moderate with most AEs connected with infusion system application (28.3% patients) including procedure pain. Serious AEs were registered in 8 patients (16.7%). 3 patients (6.3%) discontinued their participation in the study due to AEs. Mean duration of "off" periods by the end of the study decreased by 5.35±2.59 hours (p<0.001), duration of "on" periods without troublesome dyskinesia increased by 5.74±3.91 hours (p<0.001), reduction of "on" periods duration with troublesome dyskinesia became statistically significant by week 36 (p=0.020). The statistically significant improvement of UPDRS (generally and in respect to sub-scales), Clinical Global Impression, and Quality of Life scores was observed throughout the study. Levodopa dose remained stable throughout the 54 treatment weeks. Forty-three patients (93.5%) received LCIG monotherapy throughout the whole study. CONCLUSION: LCIG intrajejunal infusion during 54 weeks showed the favorable safety profile, high tolerability, and efficacy in PD motor symptoms correction.

[Modern approaches to the therapy of biliary system diseases].

The therapeutic efficacy of duspatalin was evaluated in 72 patients with chronic cholecystitis and dyskinesia of the biliary tract (BT). Supplementation of duspatalin to the combined therapy in the patients with chronic cholecystitis shown to exert a pronounced therapeutic effect. This caused positive changes in clinical symptoms and BT function and quality of life, diminished the lithogenic properties of bile.

[Topiramate in the treatment of essential tremor].

Therapeutic efficacy of topiramate in essential tremor (ET) was assessed in comparison with propranolol in two groups which included 24 and 20 patients, respectively, aged from 21 to 83 years (mean age 53 years). Along with clinical examination, a number of scales: Clinical rating scale for tremor, scale of functional disturbances and Visual-analogous scale have been administered. The efficacy of topiramate was comparable to that of propranolol in 83% and 75% cases, respectively. However topiramate has some therapeutic advantages compared to propranolol; it may be prescribed for all clinical forms regardless of sex (its efficacy is higher in women), age and illness duration, both in earlier and later onset, familial and sporadic variants of ET (propranolol is more effective in patients with family history of ET). Moreover, in contrast to propranolol, topiramate may be prescribed to patients with predisposition to arterial hypertension and bradicardia, bronchial spasms of diabetes mellitus and heart rhythm disturbances.

[Insulin edema in patients with diabetes mellitus and recent diabetic ketoacidosis (epidemiology and case reports)]. / Insulinovyi otek u bol'nykh sakharnym diabetom, nedavno perenesshikh diabeticheskii ketoatsidoz (épidemiologicheskie dannye i klinicheskie varianty).

Insulin edema (IE) has been known for a long time as one of complications caused by insulin therapy, but even today its pathogenesis stays unclear, and epidemiology unknown. IE incidence in patients over 15 years of age receiving treatment in the year 2003 for diabetic ketoacidosis (DKA) in the city of Donetsk (adult population 858200) has been retrospectively studied according to clinical archives and national diabetics register data. Presented are three own observations on the development of IE after DKA treatment. 13 (17%) out of 76 DKA patients had IE. Keeping in mind reoccurring DKA incidents--16%. During IE the known duration of Diabetes Mellitus came out to be 5 years on average, and did not differ from insulin therapy duration, whereas the Diabetes Mellitus duration in non DKA group without edemas exceeded the continuance of insulin treatment by over two years (P < 0.05).

[Echography in congenital intestinal obstruction in newborn infants]. / Ekhografiia pri vrozhdennoi neprokhodimosti kishechnika u novorozhdennykh.

The authors used echography in order to reveal typical echographic signs of high and low bowel obstruction in 51 newborns. Although the use of echography often fails to establish the real cause of the bowel obstruction, it allows the determination of its level and in general promotes making the proper diagnosis.