The human genome consists of 22,000 protein-coding genes to facilitate metabolism, while the microbiome is estimated to contribute 150-360 times more unique coding genes than the human genome itself. In this regard, it is postulated that the immunological and metabolic potential of the gut microbiota may directly impact various physiological processes, including the modulation of myocardial resistance to ischaemic reperfusion injury. Researchers posit that symbiotic microorganisms, which form the basis of probiotic preparations, have a significant impact on both normal physiological processes and pathological conditions, especially those of an inflammatory nature.

“Evolutionarily adapted probiotic microbes have a vital interest in maintaining a mutually beneficial relationship with their host. We believe that bacteria protect cardiac cells from toxic damage and the effects of oxygen deprivation by fine-tuning pro- and anti-inflammatory signaling molecules,” explains Mikhail Galagudza, Director of the Institute of Experimental Medicine.

 

In order to ascertain the cardioprotective capabilities of probiotic microorganisms, an original experimental model of polymorbidity in small rodents has been developed. This model includes primary visceral obesity (PVO), inflammatory colon disease (ICD) and antibiotic-induced dysbiosis (AID). This combination of conditions, prevalent in clinical settings, has been observed in experimental animals to be accompanied by a substantial increase in pro-inflammatory cytokine levels.

A few days before modelling myocardial infarction and AID in the acute experiment and for a further 8 days, different groups of rats with PVO were intragastrically administered different probiotic strains and strain mixtures.

Observations demonstrated that administration of a mixture of Lactobacillus acidophilus and Bifidobacterium animalis, unlike other probiotics, reduced the size of heart muscle damage caused by infarction by 10%. This enhancement in the heart health of the animals was accompanied by a reduction in the levels of pro-inflammatory cytokines and an improvement in the general condition, including the digestive system.

The scientists suggest that the mechanism of cardioprotection is based on the ability of symbiotic microorganisms to synthesize blockers of some pro-inflammatory cytokines, their receptors or to modulate the expression of their genes. The researchers hope that further research into the mechanisms of probiotic cardioprotection will help to develop new therapeutic and preventive approaches in cardiology by selecting strains for new probiotic drugs and functional foods.

Symptoms of cortisol excess are obesity (when fat is on the abdomen and face – “moon” face), high blood pressure, high blood sugar level (up to diabetes), muscle weakness (due to the protein breakdown by cortisol action), skin becomes thinner, in this connection, purple stretch marks also called striae. Immunity in patients weakens, due to this the risk of infectious diseases increases. Patients also face the risk of heart attacks and strokes, and thrombosis. Bones become brittle, spontaneous fractures, mostly the spine, are frequent. Sexual sphere of patient also suffers. In children high cortisol is often manifested by growth retardation. In the absence of diagnosis and treatment, the mortality of patients increases more than twice in comparison with the general population average mortality.

Besides the pituitary adenoma, neuroendocrine tumors can be the source of high ACTH and the cause of ACTH-ectopic syndrome; often they are localized in bronchi and lungs. They may be of very small size. Differential diagnosis of ACTH-dependent Cushing’s syndrome is very important problem. It is necessary to do careful examination of the patient with ACTH-dependent hypercorticism in order to avoid errors and, therefore, improper treatment.
Currently there is no laboratory test that could determine the source of ACTH in 100% cases. Ordinary the high dexamethasone test is used, but often its results are ambiguous. Pituitary MRI can not detect small pituitary adenoma in 100%. On the other hand, various studies show that more than 10% of healthy people have a pituitary adenoma that does not produce any hormones, so called pituitary incidentaloma. Thus, in the case of small size pituitary adenoma and/or questionable data of laboratory tests, one can not exclude that the pituitary adenoma is an accidental finding and has no any relation to ACTH hyper production. In this case, its removal will not lead to a recovery. On the other hand, if laboratory data indicate the presence of a pituitary adenoma, but the MRI can not find it, it does not mean that there is no corticotropinoma indeed.

Now there is only one method that permits to define the localization of the ACTH hyperproduction source with high sensitivity and specificity. It is the blood sampling from the vessels in which blood flows directly from the pituitary gland — so-called catheterization of cavernous and inferior petrosal sinuses with ACTH blood sampling.

This method is minimally invasive and well tolerated by patients. However, it is quite complex in terms of execution, requires appropriate technical equipment and angiosurgeon’s great experience, and therefore can be performed only in large tertiary centers.

Federal North-West Medical Research Centre is one of few centers in Russia where it is possible to perform this test in patients with suspected Cushing's disease, and the only center in Russia where not only inferior petrosal sinuses, but also cavernous sinuses catheterization is performed, the latter improves the method´s accuracy.

Under X-ray control the thin catheter via femoral vein is brought in the brain sinuses, and for monitoring the progress the radiopaque drug is periodically delivered. The patient is conscious and does not feel pain. Blood samples are taken from the both cavernous sinuses, both inferior petrosal sinuses, both internal jugular veins and postcava, and concentration of ACTH is investigated. Thus it is possible to localize if the source of ACTH hyperproduction in the pituitary or outside it. In the cases when corticotropinoma is invisible on MRI, according to the difference of ACTH levels in the right and left sinuses one may assume the localization of micro adenomas in the right or left half of the pituitary gland. Thus the new high-tech method of separate catheterization of the cavernous and inferior petrosal sinuses with blood sampling for ACTH will improve the differential diagnosis of Cushing's disease. Proper diagnosis and prompt treatment of this serious disease will reduce the risk of severe complications and save patients’ lives.

As drug carriers can be used both inorganic and organic nanoparticles. The inorganic particles can be gold, silver, iron oxides, silicon, fullerenes, nanotubes, and others. The organic vehicles are more diverse and include whole classes of organic polymers, proteins, liposomes, dendrimers, and even viruses.

Thus, nanodrugs offer new prospects for effective treatment of various pathological processes, for example: cancers, heart disease, including coronary heart disease, inflammation, etc.

Currently the Research Laboratory of Nanotechnology is actively functioning  on the basis of the Institute of Experimental Medicine of Federal North-West Medical Research Centre. The Laboratory works on the targeted drug delivery into the damaged tissue, mostly in myocardium and skeletal muscle.

A large number of organic and inorganic nanoparticles are investigated as drug vehicles; we tested their important properties and features such as toxicity, ability to eliminate from the body, and also the delivery effect. The results of these studies were published in Russian scientific journals, e.g.: “Russian Nanotechnology”, “Nanotechnics”, “Biotechnosphere” and the leading international journals, e.g.: International Journal of Nanomedicine, Materials. In 2012, we received a patent for the invention named “Cardioprotection method”.  The invention is included in the list of 100 best inventions of Russia.