[Clinical efficacy of a modern probiotic for the correction of intestinal microflora in patients with irritable bowel syndrome with diarrhea and antibiotic-associated diarrhea].

Despite the fact that dietary supplements (DS) are not medicines, an increasing number of publications testify to the effectiveness of probiotics consumed with food in the complex treatment and prevention of a number of diseases of the gastrointestinal tract, including irritable bowel syndrome (IBS) and antibiotic-associated diarrhea (AAD). The purpose of the study was to evaluate the effectiveness of the complex probiotic in the relief of diarrheal syndrome associated with intestinal microbiota dysbiosis in patients with IBS with diarrhea and AAD. Material and methods. The study included 54 patients (31 with IBS with diarrhea and 23 with idiopathic AAD) aged 18 to 50 years. All patients included in the study were prescribed 1 capsule (350 mg) of the DS Neobiotic Lactobalance® per day for 21 days. One capsule contains: bifidobacteria (Bifidobacterium longum CBT BG7, Bifidobacterium lactis CBT BL3 Bifidobacterium bifidum CBT BF3), lactobacilli (Lactobacillus acidophilus CBT LA1, Lactobacillus rhamnosus CBT LR5), lactic acid bacteria (Streptococcus thermophilus CBT ST3), fructooligosaccharides, vitamin C. The daily intake of bifidobacteria was 8.7×108 CFU, lactobacilli - 6.1×109 CFU, lactic acid bacteria 3.1×108 CFU and vitamin C - 12 mg. The severity of symptoms was assessed in points (from 0 to 7 points) using the GSRS questionnaire (Gastrointestinal Symptom Rating Scale). All patients underwent a microbiological analysis of feces with an assessment of the degree of dysbiosis before and after the administration of DS. Results. In patients with IBS with diarrhea, the assessment of the manifestations of diarrheal syndrome according to the GSRS questionnaire decreased statistically significantly from 17 to 6 points (2.9 times), abdominal pain - from 12 to 4 points (3.0 times) and dyspeptic syndrome - from 8 to 3 points (in 2.7 times). In patients with AAD, also according to the GSRS questionnaire, the manifestations of diarrheal syndrome decreased statistically significantly from 13 to 3 points (4.3 times), abdominal pain - from 4 to 1 points (4.0 times) and dyspepsia syndrome - from 5 to 2 points (in 2.5 times). Against the background of DS intake, according to the data of bacteriological examination of feces, intestinal microbiota normalized by day 21 due to an increase in the number of lacto- and bifidobacteria (p=<0.05). Conclusion. The study showed that the DS Neobiotic Lactobalance® contributes to the normalization of the intestinal microbiota and reduces the severity of clinical manifestations (diarrheal disorders or manifestations of diarrhea) in IBS and idiopathic AAD.

[Myostatin - a modern understanding of the physiological role and significance in the development of age-associated diseases.]

Myostatin is a protein belonging to the myokine class, the family of transforming growth factors ß (TGF-ß). The review article, based on the analysis of literature data, shows the key role of myostatin in the development of senile sarcopenia and cachexia in various pathological conditions, such as cancer, chronic heart failure, chronic renal failure, COPD, etc. The article discusses the structure of myostatin, provides a detailed diagram of the synthesis and activation of myostatin, the ways of implementing the mechanism of action as a negative regulator of muscle growth and differentiation in these pathological conditions. The main physiological properties and clinical significance are highlighted. Exogenous and endogenous factors regulating myostatin expression and possible mechanisms of their action are considered.

Effects of low-dose, noncytotoxic, intraarticular liposomal clodronate on development of erosions and proteoglycan loss in established antigen-induced arthritis in rabbits.

OBJECTIVE: To assess the clinical and histologic effects of an intraarticular application of low-dose (non-cytotoxic) liposomal clodronate in established antigen-induced monarthritis (AIA) in rabbits. METHODS: AIA was monitored by assessments of joint swelling, C-reactive protein levels, and radiographic changes in 17 NZW rabbits for 8 weeks during the course of weekly intraarticular injections of liposomal clodronate (0.145 mg/injection, low dose) or "empty" liposomes. The contralateral knee was injected with liposome buffer alone as the control. End-point analyses included macroscopic joint examination, immuno- and TUNEL staining, Safranin O staining/microspectrophotometry, and tumor necrosis factor alpha (TNFalpha) convertase enzyme (TACE) inhibition assay. RESULTS: Liposomal clodronate-treated rabbits showed a reduction and delay in joint swelling during the first 3 injections. Expression of matrix-bound (solubilized) TNFalpha, lining cell hyperplasia, and levels of RAM-11+ macrophages were low in the synovium of the liposomal clodronate treatment group, but the proportion of apoptotic lining cells was not affected. The radiologic score was low at the end of weeks 2 and 4, but at 8 weeks, no difference, compared with controls, was found in pannus formation or in the extent of joint erosion; also, joint swelling was higher than before initiation of treatment. Injections of liposomal clodronate prevented cartilage proteoglycan loss, which was significant in the superficial zone only. TACE activity was not inhibited by clodronate. CONCLUSION: Liposomal clodronate had temporary antiinflammatory and antierosive effects on established AIA in rabbits. Over the long-term, the loss of cartilage proteoglycans was halted. This observed treatment effect may be related to the inhibition of TNFalpha production and processing in the synovium.

Fatigue and health profile in sicca syndrome of Sjögren's and non-Sjögren's syndrome origin.

OBJECTIVE: To assess the health status and fatigue in sicca patients with or without Sjögren's syndrome (SS) and to test whether the immune-inflammatory activity or the extent of the disease predict fatigue in SS. METHODS: The Medical Outcomes Study Short-Form General Health Survey (MOS SF-36) was used in 1 degree SS (n = 90), 2 degrees SS (n = 24), non-SS patients with sicca symptoms (n = 15) and healthy population controls (n = 126). Laboratory values and clinical findings were used to predict fatigue in SS. RESULTS: 74% of the SS and 80% of the non-SS sicca patients felt themselves tired. Vitality score values were 40.2 +/- 20.3 in 1 degree SS, 42.1 +/- 20.6 in 2 degrees SS and 29.0 +/- 15.8 in non-SS. The health profiles were similar in 1 degree and 2 degrees SS, worse (p < 0.001) than in normal controls, but in most aspects better than in non-SS sicca patients. In SS neither hemoglobin, ESR nor CRP predicted fatigue. Surprisingly, high serum IgG (p < 0.05), antinuclear antibodies (ANA) (p < 0.01) and SS-A antibodies (p < 0.05) values correlated positively with vitality. The number of disease manifestations correlated negatively with vitality (p < 0.004). The total number of disease manifestations, and ANA and/or SS-A autoantibodies were the best predictors of fatigue, but explained it only to 17-57%. CONCLUSION: Patients with fatigue and perceived ill health but without fibromyalgia had sicca symptoms and low basal tear and salivary secretion rates, indicating that cortical events can lead to a SS-like sicca syndrome. Even in SS fatigue is only in part explained by clinical disease manifestations and laboratory tests assessing inflammation and autoimmunity. Fatigue in both SS and non-SS sicca syndrome more likely correlates to other features, such as neuroendocrine aspects of the disease.

Gly-X-Y repeat sequences in the treatment of active rheumatoid arthritis.

The aim of the present study was to examine if oral administration of Gly-X-Y repeat sequences alleviates disease activity in rheumatoid arthritis (RA). The study had a randomized, placebo controlled and double blind design with a wash-out/cross-over between the two 3-months long treatment periods. A total of 40 patients entered and 36 patients fulfilled the study, among them 16 started with the active drug and 20 with a placebo. Disease activity score (DAS) was used as the primary outcome measure with several secondary outcome variables. Type I or alpha error of 0.05 was accepted and the power (= 1-beta) was set to 80%, which according to the power analysis was also achieved. With active drug treatment, joint swelling score (54 count; P < 0.001), Ritchie's index (P < 0.01) and DAS (P < 0.001) improved. HAQ also improved (P < 0.05), but there was no improvement in the subjective condition of the patients as measured with the self-reported Pain Disability Index and Comprehensible Psychopathological Rating scale questionnaires. Apparently, 5/36 patients had a response of > or = 1.2 in DAS and 33/36 changed for the better; DAS impaired only in 3/36 patients during the active drug treatment When the stringent EU response criteria were applied and the results were compared to the placebo group, the response was not clinically significant. We conclude that Gly-X-Y repeat sequences are not effective as used in the present study. However, this does not definitely disprove the value of the Gly-X-Y repeat sequences, because confounding effects of dosage, concomitant medication and excessive degradation of the linear Gly-X-Y sequences in the stomach, gut or by phagolysosomes could not be adequately controlled. The discrepancy between the favourable effects in the preliminary, open pilot study and the controlled clinical trial emphasizes the value of the DAS, EU response criteria and adequately administered controlled clinical studies.

Aberrant vascularity and von Willebrand factor distribution in inflamed synovial membrane.

OBJECTIVE: Von Willebrand factor (vWF) is an adhesive glycoprotein produced and secreted constitutively by endothelial cells. vWF is released upon endothelial stimulation and/or vascular injury, and mediates adhesion and aggregation of platelets. Our aim was to quantify synovial vasculature and to evaluate vWF distribution in situ in synovial membranes in various arthritides. METHODS: Immunohistochemical staining of vWF in synovial membranes from patients with rheumatoid arthritis (RA) (N = 9), psoriatic (PsA) (N = 3), and reactive (ReA) (N = 4) arthritis, and from 6 noninflammatory controls: osteoarthritis (N = 1), chondromatosis (N = 1), meniscus lesion (N = 4). Morphometric assessments were performed with an image analyzer. RESULTS: In RA, mean number of blood vessels/mm2 in the thickened synovium was relatively low (131 +/- 57 vs control 257 +/- 115, p = 0.0137, ReA 346 +/- 83, p = 0.0002, PsA 434 +/- 157, p = 0.0127). In particular, the superficial layer, corresponding to the thickness of normal synovial membrane (i.e., 56 +/- 5 microns), was sparsely vascularized (70 +/- 37 in the superficial vs 219 +/- 104 in the deeper layer, p = 0.0047). Synovial thickening was not seen in ReA and PsA. In accordance with its constitutive metabolism, vWF was found in the endothelial cells, inside the blood vessels, and in the subendothelium. In addition, RA was characterized by weak endothelial immunoreactivity and perivascular vWF. In ReA, perivascular vWF staining was visible in areas of inflammatory cell infiltrates. CONCLUSION: Morphometric findings indicate decreased vascularization of the superficial synovial membrane in RA. Second, vWF may play a role in the inflammatory/reparative responses in synovium in RA and ReA, which were characterized by vascular stimulation/injury and abnormal vWF distribution.

Mast cells in loosening of totally replaced hips.

This study evaluated mast cells in tissue around loose total hip implants. Interface and pseudocapsular tissues were obtained from 6 patients with a loose hip prosthesis. Mast cells were labeled with monoclonal mouse antihuman antibodies against tryptase and chymase in avidin-biotin-peroxidase complex staining and were quantitated morphometrically by means of a semiautomatic Kontron image analyzer. Almost all mast cells in situ were chymase-positive and tryptase-positive connective tissue cells. The mean number of such cells per mm2 of tissue increased in this rank order: interface (9.98 +/- 5.03 cells) < pseudocapsule (15.85 +/- 4.99 cells) < control knee synovium (25.08 +/- 8.64 cells). Mast cells in periprosthetic tissue, in contrast to normal knee synovial tissue, exhibited granule release. Mast cells around loose hip prostheses appeared to be activated by connective tissue mast cells. These were found in diminished numbers and in a degranulated state in the interface tissue between implant and bone. Mast cell activation in loco may thus lead to significant local production and/or release of proinflammatory mast cell mediators. Prevention of mast cell activation (degranulation) could prove useful in the postponement of loosening of the totally replaced hip.

Periprosthetic microvasculature in loosening of total hip replacement.

This study was performed to quantitate vascularity in periprosthetic tissues of loose total hip replacements (THRs), because most likely revascularization and endothelial cells are important for implant osseointegration and loosening. Interface and pseudocapsular tissue samples obtained from loose THRs were stained with an immunohistochemical labelling (ABC technique) for von Willebrand factor. Non-inflammatory synovial samples served as controls. The results were quantitated by morphometry using the Kontron image analysis system. Evaluation of the mean endothelial index (EI; positively stained area micron/mm2 of tissue) revealed that in the control samples synovium was better vascularized than was the case in the cellular areas of the periprosthetic pseudocapsule (P = 0.0008) and interface (P = 0.0004) of loose THRs. There was no significant difference between mean EI of cellular areas in the interface and that of the pseudocapsule (P = 0.24). In the interface the vascularity was irregular. Vascular injury and decreased blood supply seem to occur at the implant-host interface, which may be one of the reasons for insufficient implant osseointegration and loosening.