Optimization of treatment of patients with chronic cardiac insufficiency of the ischemic genesis and hobnail liver

Clinical efficacy of combined therapy including the use of rifaximin and L-ornithin-l-aspartate, as well as the dynamics of the biochemical indices, the manifestation levels of portal-systemic-encephalopathy and intestinal microbiocynosis were investigated in patients with chronic cardiac insufficiency of ischemic genesis and hobnail liver. The combined therapy resulted in improvement of the patients clinical state, lower levels of the portal-systemic encephalopathy manifectation by decreasing hyperammonium, normalization of the large intestine microflora, and blood serum biochemical parameters.     

Indications for treatment

Parasites produce damage to man by 1) Consumption of nutrients 2) Destruction of tissues 3) Traumatic lesions 4) Toxic action 5) Immunoallergic reactions. Humans react against parasitic attack with their natural and acquired defences. Age, race, sex, genetic endowment and nutritional status are some of the factors which influence natural immunity. Acquired cellular immunity is responsible for the state of premunition which avoids superinfection in some parasitoses. The development of an infection or of the clinical disease in an individual will depend on the interaction between the aggressive factors of the parasite and the defensive capacities of the host. In the great majority of cases an equilibrium will result: in other words, an infection. When there is a great load of parasites with great pathogenicity affecting a susceptible host, a disease will develop which can eventually result in death. Treatment should be administered on the basis of clinical, epidemiological or prophylactic considerations. In amebiasis the virulence of the races is the main parasitic factor. The difference between virulent races is quantitative and not qualitative and can be demonstrated by phagocytosis of red blood cells, “toxin” production and by inoculation into the liver of newborn hamsters. The cytotoxin has at least two components: collagenase and amebapore.The nutritional status, intestinal lumenal pH and redox potential, secretory IgA and mucus and plasma complement are some of the host factors which influence the pathogenicity of amebae. Curative treatment is indicated on intestinal or extraintestinal invasive amebiasis. Prophylactic treatment should be administered to infected food handlers and infected persons in developed countries. In toxoplasmosis, curative treatment is indicated in patients with clinical manifestations of acquired or congenital infection, in acute, sub-acute or chronic, reactivated periods. The clinical symptomatology must be correlated with serological testing which indicates “activity”. In some acquired lymph node toxoplasmosis, without general compromise, asthenia, adynamia or fever, treatment is not needed because of its good prognosis. Chronic inactivated cases, or sequelae do not require treatment. Prophylactic treatment is indicated: in: 1) Pregnant women with seroconversion to avoid congenital infection. 2) In apparently healthy children with asymptomatic congenital infection, to avoid late ocular lesions. 3) In individuals who receive immunosupressive therapy and have serological evidence of toxoplasmosis activity.In the larva migrans syndrome, treatment is indicated in patients with symptomatology oreosinophilia. The therapy may produce remission of the clinical picture or of the eosinophilia.     

Telmisartan in the treatment of hypertension in patients with chronic renal insufficiency

The primary aim of this study was evaluation of the efficacy of telmisartan (angiotensin II receptor blocker- AT(1) blocker) on blood pressure in 10 patients with renal impairment in moderate or advanced stages of renal insufficiency and not dependent on haemodialysis. Its effect on proteinuria, renal function (represented by serum urea, creatinine, glomerular filtration), evaluation of overall therapy compliance in comparison with a previously prescribed angiotensin converting enzyme inhibitors (ACEI) were secondary aims. Considering the presence of left ventricle hypertrophy in all patients as a marker of hypertensive cardiopathy, the effect of telmisartan therapy on non-invasive cardiovascular parameters (ECG, echocardiography, and assessment of heart rate variability-HRV) was also evaluated. The study group involved 10 hypertensive patients (6 women, 4 men) with diabetic and non-diabetic renal impairment, proteinuria above 1 g/24 hours, hypertensive cardiopathy and intolerance of ACEI (cough). Telmisartan was added to their long-term antihypertensive combination therapy in a dose of 40 mg for the first 14 days, after which the dose increased to the maximal of 80 mg. The average initial daytime systolic blood pressure (SBP) was 149 +/- 19.7 mm Hg, average night-time SBP 145 +/- 23.0 mm Hg, average initial daytime diastolic BP (DBP) 90.6 +/- 2.5 mm Hg, night-time DBP 88.9 +/- 13.5 mm Hg. Average initial serum creatinine was 207.2 +/- 48.5 micromol/l, urea 15.1 +/- 4.4 mmol/l, GF 0.5 +/- 0.1 ml/s. Echocardiography revealed left ventricular (LV) hypertrophy with well preserved systolic and moderately impaired diastolic LV function. Also the HRV assessment revealed impaired neurovegetative (e.g. sympathovagal) balance. After 1 year of combination therapy with telmisartan, there was a clearly significant reduction in both SBP and DBP in both day and night-time (SBP daytime 149.6 vs.116.6 mm Hg, night-time 145.8 vs. 129.5 mm Hg; DBP daytime 90.6 vs. 83.5 mm Hg, night-time 88.9 vs. 79.3 mm Hg) and proteinuria (2.37 vs. 1.27 g/24 hour, p < 0.05). There were no significant changes in serum creatinine, urea values, and LV functions. On the other hand, further progression of the sympathovagal balance impairment was noted (continuing reduction of HRV in 9 from 10 patients), which can be described as the priority finding. The total compliance of telmisartan therapy was very good and without adverse clinical side effects. In conclusion - telmisartan reduces blood pressure and proteinuria safely and effectively in patients with various types of nephropathy in moderate or advanced stages of renal insufficiency.     

Lipid peroxidation in cardiac insufficiency

Peroxidation of lipids was studied in patients with heart failure after coronary heart disease and acquired valvular diseases. Even at early stages of the heart failure an increase in the concentration of dien conjugates, malonic dialdehyde and intensification of the peroxidation of blood lipids under stimulation by bivalent iron have been revealed. These changes do not depend on reasons which caused heart failure.     

Proteasome functional insufficiency in cardiac pathogenesis

The ubiquitin-proteasome system (UPS) is responsible for the degradation of most cellular proteins. Alterations in cardiac UPS, including changes in the degradation of regulatory proteins and proteasome functional insufficiency, are observed in many forms of heart disease and have been shown to play an important role in cardiac pathogenesis. In the past several years, remarkable progress in understanding the mechanisms that regulate UPS-mediated protein degradation has been achieved. A transgenic mouse model of benign enhancement of cardiac proteasome proteolytic function has been created. This has led to the first demonstration of the necessity of proteasome functional insufficiency in the genesis of important pathological processes. Cardiomyocyte-restricted enhancement of proteasome proteolytic function by overexpression of proteasome activator 28α protects against cardiac proteinopathy and myocardial ischemia-reperfusion injury. Additionally, exciting advances have recently been achieved in the search for a pharmacological agent to activate the proteasome. These breakthroughs are expected to serve as an impetus to further investigation into the involvement of UPS dysfunction in molecular pathogenesis and to the development of new therapeutic strategies for combating heart disease. An interplay between the UPS and macroautophagy is increasingly suggested in noncardiac systems but is not well understood in the cardiac system. Further investigations into the interplay are expected to provide a more comprehensive picture of cardiac protein quality control and degradation.