Time-dependent cytokines changes in ultra-rush wasp venom immunotherapy.

Venom immunotherapy (VIT) represents a potential therapeutic approach for the management of venom allergies, aiming to modify the immune response to venom allergens and enhance its precision. Previous studies have demonstrated that VIT induces a shift in T helper cell responses from Th2 to Th1, characterized by the production of IL-2 and interferon-gamma by CD4+ and CD8+ cells. In order to explore long-term pathways following VIT treatment and verify potential new outcomes, the serum concentrations of 30 cytokines were assessed in a cohort of 61 patients (18 control, 43 study group) exhibiting hypersensitivity to wasp venom. Cytokine levels were measured at 0, 2, 6, and 24 weeks after the initiation phase of VIT in the study group. The present study found no significant alterations in the levels of IL-2 and IFN-γ in the peripheral blood following VIT. However, a noteworthy finding was the substantial increase in the concentration of IL-12, a cytokine capable of promoting the differentiation of Th0 cells into Th1 cells. This observation supports the involvement of the Th1 pathway in the desensitization process induced by VIT. Additionally, the study revealed a significant rise in the levels of IL-9 and TGF-ß after VIT. These cytokines may play a role in the generation of inducible regulatory T (Treg) cells, indicating their potential importance in the immune response to venom allergens and the desensitization process associated with VIT. Nevertheless, further investigations are required to comprehend the underlying mechanisms driving the VIT process comprehensively.

Spleen content of selected polyphenols, splenocytes morphology and function in mice fed Rhodiola kirilowii extracts during pregnancy and lactation.

UNLABELLED: The genus Rhodiola (Crassulaceae) consists of many species, growing mainly in Asia and traditionally used as adaptogens and anti-inflammatory drugs. In order to elaborate herbal immunostimulator which could be safely given to pregnant women, we performed a study on immunotropic effects of feeding pregnant and lactating mice Rhodiola kirilowii extracts. This paper presents the results of the first part of our study - spleen content of selected polyphenols, spleen cellularity, splenocytes phenotype and their response to mitogens. Experiments were performed on adult inbred females of Balb/c strain, mated with adult males. Females, since copulatory plug was noted, up to the 28-th day after delivery were fed daily with 20 mg/kg b.m. water (RKW) or hydro-alcoholic (RKW-A) extracts of Rhodiola kirilowii. RESULTS: 1. Significantly lower proportion of pregnant mice in experimental groups than in the control. 2. Cellularity of spleen and flavonol quercetin spleen concentration were significantly lower in experimental groups in comparison to the controls. 3. Flavanols ((+)-catechin and epicatechin) levels were significantly higher in the spleens of experimental mice than in the controls. 4. Positive correlation between spleen cellularity and quercetin, and negative correlation between spleen cellularity and epicatechin content were observed. 5. Spleen mass and spleen lymphocytes phenotype and proliferation in RKW and RKW-A fed mice did not differ from the control. These results, together with suspicion of some embryo-toxicity, are worrying and eliminate the possibility of use Rhodiola kirilowii extracts for long-term treatment in pregnant females.

Inhibitory effect of herbal remedy PERVIVO and anti-inflammatory drug sulindac on L-1 sarcoma tumor growth and tumor angiogenesis in Balb/c mice.

Anticancer activity of many herbs was observed for hundreds of years. They act as modifiers of biologic response, and their effectiveness may be increased by combining multiple herbal extracts . PERVIVO, traditional digestive herbal remedy, contains some of them, and we previously described its antiangiogenic activity. Numerous studies documented anticancer effects of nonsteroidal anti-inflammatory drugs. We were the first to show that sulindac and its metabolites inhibit angiogenesis. In the present paper the combined in vivo effect of multicomponent herbal remedy PERVIVO and nonsteroidal anti-inflammatory drug sulindac on tumor growth, tumor angiogenesis, and tumor volume in Balb/c mice was studied. These effects were checked after grafting cells collected from syngeneic sarcoma L-1 tumors into mice skin. The strongest inhibitory effect was observed in experimental groups treated with PERVIVO and sulindac together. The results of our investigation showed that combined effect of examined drugs may be the best way to get the strongest antiangiogenic and antitumor effect.

Suppressive effect of electromagnetic field on analgesic activity of tramadol in rats.

The electromagnetic fields (EMFs) have been shown to alter animal and human behavior, such as directional orientation, learning, pain perception (nociception or analgesia) and anxiety-related behaviors. The aim of this study was to evaluate the influence of electromagnetic fields of high-frequency microwaves on pain perception and anti-nociceptive activity of tramadol (TRAM) - analgetic effective in the treatment of moderate to severe acute and chronic pain states. Electromagnetic fields exposures of a)1500 MHz frequency and b) modulated, 1800 MHz (which is identical to that generated by mobile phones) were applied. Paw withdrawal latency (PWL) to thermal stimulus was measured in vehicle or tramadol (TRAM) treated animals before and after 30, 60 and 90 minutes from injections. The differences in the level of pain (PWL) between control group and rats exposed to EMF alone in three measurements, were not observed. Tramadol alone significantly increased PWLs to thermal stimulus in comparison to vehicle results at 30 (p < 0.001) and 60 minutes (p < 0.05) after drug injection. EMF exposure of both frequencies transiently suppressed analgesic effect of tramadol, significantly reducing paw withdrawal latency in animals treated with this drug at 30 minutes from the drug injection.

Effect of three common SNPs in 5'-flanking region of LEP and ADIPOQ genes on their expression in Polish obese children and adolescents.

Genes encoding adipokines are considered as candidates for human obesity. In this study we analyzed the expression of leptin (LEP) and adiponectin (ADIPOQ) genes in relation to common 5'-flanking or 5'UTR variants: -2548G>A (LEP), 19A>G (LEP) and -11377C>G (ADIPOQ) in Polish obese children and adolescents. Relative transcription levels in the subcutaneous adipose tissue (real time RT-PCR) and serum protein concentrations (RIA) were measured in 48 obese subjects with known genotypes at three polymorphic sites and in five non-obese controls. None of the studied polymorphisms altered significantly the expression. Significantly elevated relative transcription levels of the LEP gene (P < 0.05) and serum leptin concentrations (P < 0.01) were recorded in obese patients, when compared with the non-obese controls, but such differences were not found for the ADIPOQ gene. Interestingly, the leptin to adiponectin protein concentration ratio (L/A) was approximately sevenfold higher in obese children and adolescents when compared with the non-obese controls (P < 0.001). Taking into consideration the observed relationship between the genotypes and the gene expression level we suggest that these SNPs are not conclusive markers for predisposition to obesity in Polish children and adolescents. On the other hand, we confirmed that the leptin to adiponectin gene expression ratio (L/A) is an informative index characterizing obesity.

Dose-dependent in vivo effect of Rhodiola and Echinacea on the mitogen-induced lymphocyte proliferation in mice.

Echinacea purpurea (EP) and Echinacea angustifolia (EA) are ones of the most important world's herbs with immunotropic activity. They were traditional medicinal plants used by North American Indians for the treatment of various illnesses. Now they are cultivated in many countries and are used mainly to treat respiratory tract infections. Rhodiola rosea (RR) and Rhodiola quadrifida (RQ) are medicinal plants originated from Asia and used traditionally as adaptogens, antidepressants, and anti-inflammatory remedies. We previously reported, that extracts of underground parts of RR and RQ exhibited immunotropic activity. We have demonstrated in pigs that in vitro RR or RQ supplementation of blood lymphocyte cultures stimulated T cell proliferative response to Con A in lower, and inhibited it in higher Rhodiola extract concentrations. The aim of this work was to evaluate the in vivo effect of these herbal remedies on the in vitro proliferative response of mouse splenic lymphocytes to another T-cell mitogen- Phaseolus vulgaris haemagglutinin (PHA). We have found significant stimulation of proliferative response, in comparison to the controls, in mice fed lower doses of tested remedies, and inhibition, no effect or lower stimulation, in mice fed higher doses of these drugs.

A modified technique of delayed basilic transposition - initial results.

The radiocephalic wrist fistula remains the "gold standard" for primary vascular access placement according to NKF -DOQI guidelines. However, liberal inclusion criteria for dialysis therapy, as well as increasing longevity and prevalence of diabetes, have led to an increased number of patients with distal vessels unsuitable for vascular access creation. Another available location, and one used with increasing frequency, is the anterior cubital fossa. Arteriovenous anastomoses in this location leads to the development of two possible vascular accesses: cephalic and basilic. The basilic vein needs to be transposed to the anterior aspect of the arm. However, this procedure is technically difficult and carries a high risk of complications, often associated with axial torsion or kinking of the transposed vein during placement in the subcutaneous tunnel. The authors propose a simple technical modification which minimizes the risk of these complications. The main advantage is the prevention of axial torsion and kinking, as well as avoiding venous stenosis by transecting the vein at its widest point.

Vascular access for chronic dialysis using the superficial femoral vein.

PURPOSE: We report our experience in using the superficial femoral vein to create hemodialysis (HD) arteriovenous (AV) fistulas. Surgery was performed on six patients (four female, two male). Indications for surgery included previous fistula loss, graft infection and exhaustion of typical shunt sites. METHODS: The femoral vein was evaluated preoperatively, by Doppler ultrasound, harvested by one long incision on the anteromedial surface of the thigh, followed by suction drainage. In four patients, harvested veins were transplanted in the arm between the brachial artery and axillar vein, followed by an end-to-side anastomosis. In two patients, the venous graft remained on the anterior surface of the thigh. In those patients, they were extended with either a piece of polytetrafluoroethylene (PTFE) graft or the saphenous vein. RESULTS: Follow-up ranged between 14 months and 2 yrs, ensuring proper dialysis. Two patients presented with complications, including lower leg swelling and axillary lymphorrhea, which subsided spontaneously. CONCLUSIONS: We recommend this type of AV fistula, especially in difficult cases, where all other classical vascular approaches have been used. However, the procedure is time consuming and requires experience in vascular surgery.

Competition of IL-1 and IL-1ra determines lymphocyte response to delayed stimulation with PHA.

BACKGROUND: Human peripheral blood mononuclear cells (PBMC) left in microcultures for 24h without mitogen do not respond to subsequent stimulation with PHA. They regain reactivity if the native culture medium is absorbed with other party lymphocytes or partially replaced with the medium from a PHA-stimulated culture. The observations suggest that, during the incubation, some inhibitory agent had accumulated in the culture medium. AIM: The study was performed to determine the nature of the observed phenomenon in respect of the possible role of monocytes and their products IL-1 and IL-1 receptor antagonist (IL-1ra), and to test for immunodiagnostic purposes the significance of quantifying the lymphocyte response to delayed stimulation with PHA in patients suffering from inflammatory prosesses. METHODS: Lymphocyte response to delayed stimulation with PHA, calculated as the lymphocyte-monokine interaction (LM) index, was determined in the microcultures of PBMC isolated from the blood of healthy donors or of patients with acute tonsilitis. The values of LM indices were compared with the ratios of IL-1ra/IL-1beta concentration estimated by enzyme-linked immunosorbent assay method in the culture supernatants. The influences of exogenous IL-1beta, IL-1ra, anti-IL1ra antibodies and antibiotic cefaclor on the monokine concentrations and on the values of LM index were tested. RESULTS AND CONCLUSIONS: The results show that the level of lymphocyte response to delayed stimulation with PHA (LM index) is inversely proportional to the ratio of IL-1ra/IL-1beta concentration in the culture. The low LM values at high IL-1ra/IL-1beta ratios in PBMC cultures from healthy donors, reversed proportions found in patients' PBMC (acute tonsilitis), and the cefaclor-induced reduction of LM value with correlated increase of the IL-1ra/IL-1beta ratio suggest that the LM assay may prove to be useful for immunodiagnostic purposes.

Desirable and undesirable immunotropic effects of antibiotics: immunomodulating properties of cefaclor.

The effect exerted on complex immunoregulatory functions of the immune system is an important criterion when selecting an antibiotic. When assessing the effect of an antibiotic on the immune system, one should also take into consideration the existence of functional relationships between the immune system and the nervous and hormonal systems. Among these three systems, there are common factors that modify biological processes. This makes it possible for the antibiotic not only to interact directly with the elements of the immune system, but also to exert indirect influences on potential neurotropic and endocrinotropic effects of the drug. Besides highly effective bactericidal activity, cefaclor demonstrates the ability to exert a favorable effect on some of the specific and non-specific immune responses and immunoregulation mechanisms, which may be important from a clinical point of view. Cefaclor enhances phagocytosis and bactericidal activity of granulocytes and macrophages, and favorably modifies the cooperation of monocytes and T lymphocytes. In this way, it corrects, both in vivo and in vitro, the immunoregulatory disturbances induced and aggravated by an infection. This effect is reflected by an improvement in the impaired immunoregulating activity of T lymphocytes, and is manifest both as an increase in suppressive activity and a correction of the monokine level ratio in relation to the decrease of proinflammatory monokine IL-1 and a relative increase of antiinflammatory IL-1ra. By normalizing the disturbed immunoregulation mechanism, cefaclor enhances the protective potential of the immune reaction while it also reduces the risk of immunogenic clinical complications such as persistent inflammatory conditions and allergic and/or autoaggressive responses. Such immunomodulating properties of cefaclor may be useful in the clinical treatment of patients with immune disorders leading to chronic inflammation and secondary allergic or autoaggressive reactions.

[Polish multicenter study on diabetes type I incidence in he age group 0-14 between 1998 and 1999]. / Wieloosrodkowe badania nad zapadalnoscia na cukrzyce typu 1 w grupie wiekowej 0-14 lat w Polsce w latach 1998-1999.

The increase in diabetes type 1 incidence observed in various centers in Poland and the need for a centralized study covering large population have resulted in the construction of a standardized registry of type 1 diabetes in 1998 within the Polish Multicenter Study in Diabetes Epidemiology. The aim of the study was to present the incidence rates of type 1 diabetes in the age group 0-14 in 7 distinct regions of Poland (Krakow, Wroclaw, Warsaw, Bialystok, Poznan, Rzeszow and Olsztyn centers) with over 30% of the Polish population at risk in 1998 and 1999. The data for the standardized registry were obtained prospectively from paediatric hospital wards and diabetes outpatient units. The incidence rates calculated in 1998 showed the highest value of 14.6 and 14.5/100,000 for Olsztyn and Warsaw, and the lowest (8.4/100,000) for Poznan center. In 1999 the highest value of 14.7/100,000 was noted in Krakow and the lowest (9.3/100,000) in Poznan center. The differences in diabetes type 1 incidence rates between age groups 0-4, 5-9 and 10-14 were found to be significant (p < 0.0005) and were also significant when incidence rates were compared between males and females in these age groups in the whole study area in 1998-1999 (p = 0.002 and p = 0.015 respectively).

[Involvement of WT1 gene expression in regulation of P53 and MDM2 proteins function in acute lymphoblastic leukemia]. / Rola ekspresji genu WT1 w regulacji funkcji bialek P53 i MDM2 w ostrej bialaczce limfoblastycznej.

Using sensitive techniques such as reverse transcription polymerase chain reaction (RT-PCR) the expression of WT1 gene in acute lymphoblastic leukemias (ALL) is indicated. High level of mRNA WT1 was only observed in ALL cases with leukemic cells characterized by P53- and MDM2-positive staining in cytometric analysis. The overexpression of P53 protein has not been induced by P53 gene abnormalities and MDM2 protein synthesis was independent from respective gene amplification. The data suggest that WT1 may play a distinct role in the pathophysiology of acute leukemias. It can regulate the function of the main oncoprotein network factors--P53 and MDM2 proteins. There was concluded that the most important mechanism of tissue P53-immunopositivity was connected with the P53 interactions with other oncoproteins, especially with MDM2 and WT1. They have caused different effects in particular cases and several phenotypes of leukemic cells were described. However, the negative tissue staining with anti-P53 monoclonal antibodies can not be evidence of the proper P53 protein function. The immunohistochemical estimations of the P53 level in the cells are insufficient for diagnostic and clinical evaluations. Molecular analyses of P53 and MDM2 genes, as well the WT1 gene transcription, are necessary for the proper characterisation of functional and structural status of P53.

[Immunotropic effects of electromagnetic fields in the range of radio- and microwave frequencies]. / Immunotropowe wplywy pól elektromagnetycznych z zakresu radiofal i mikrofal.

On the grounds of reviewed literature and the results of own experiments, the authors present current views on the possible immunotropic influence of low energy electromagnetic fields, in the range of radio- and microwave frequencies. They conclude, that a more systematic and multidisciplinary investigations should be undertaken, comprising the wide spectrum of immune homeostatic tasks, including defensive, immunoregulatory and pro-regenerative capabilities of immune system exposed to rapid environmental spread of different electromagnetic emitters.

[Glucosamine in the blood serum of young people with diabetes mellitus type 1]. / Glukozamina w surowicy krwi mlodziezy z cukrzyca typu 1.

The observations of some authors have shown that prolonged hyperglycemia may increase the process of hexosamin biosynthesis. The purpose of our study was to determine glucosamine levels in young patients with poorly controlled diabetes mellitus type 1. The study group consisted of 31 girls and boys whose ages ranged from 7 to 17 and who were newly diagnosed with type 1 diabetes mellitus. The diagnosis of diabetes mellitus was based on increased anti-insulin antibody levels, raised glycated hemoglobin and glucose concentrations and decreased insulin and C-peptide levels. In the studied group impairments in acid-base homeostasis as well as a correlation between the degree of blood acidification and free fatty acids, total cholesterol, and triglyceride levels were found. Despite evident hyperglycemia observed in all patients, glucosamine levels were within the normal range. Based on the present and previous investigations, where we observed increased hexosamine levels only in patients with hyperinsulinemia, we can draw the conclusion that increased enzymatic glycation of proteins requires not only increased glucose but also insulin access.

[Sarcoidosis of the paranasal sinuses]. / Sarkoidoza nosa i zatok szczekowych.

The authors described diagnostics difficulties, clinical features and treatment of this disease. The treatment is insufficient, but only interventional, although the clinically dominating symptoms may be due to a chronic disease inside of the sinuses and they are known to be caused by specific disorders in immunology. Immunosuppression, using prednisone, and reestablishing sinus ventilation and drainage via natural ostia is the basis of treatment, but it does not lead to recovery. Two rare cases of paranasal sinuses sarcoidosis are described.

Retroperitoneal rupture of abdominal aortic aneurysms.

OBJECTIVE: About 40% of patients with ruptured abdominal aortic aneurysm (AAA) die before admission to the hospital. The next 40-50% of patients who reach a hospital die in the perioperative period or within 30 days after surgery. Two groups of patients with ruptured AAA can be distinguished: first-with intra-abdominal rupture, second-with retro-peritoneal rupture. The aim of the study was a retrospective analysis of the treatment results in patients with retro-peritoneal rupture of AAA. MATERIAL AND METHODS: 78 patients underwent a surgical procedure between 1.01.1985 and 30.10.1996. 78 patients (68 men and 10 women), mean age 67.6 (53-94) were included in this study. Based on diagnostic and surgical procedures, two periods of treatment can be distinguished. In the first period of the time from 1.01.1985 to 31.12.1992 patients were operated on immediately after admission to the hospital. In the second period from 1.01.1993 to 31.10.1996 patients were admitted to Intensive Care Unit. In this unit patients were intensively treated and prepared for surgical procedure. During this time the computerized tomography scanning (CT) was performed. RESULTS: In the first period the perioperative mortality was 75%. In the second period the perioperative mortality was 41.3%. DISCUSSION: The 1.5-2 hours postponement of operative procedure of the patients with retro-peritoneal rupture of AAA can decrease perioperative mortality. During the time patients were intensively treated and prepared for surgical procedure and CT examination enabled to choose proper surgical technique.

Skeletopy of the common iliac arteries in human fetuses.

Using radiological method, seventy human fetuses were studied for the relation of the common iliac arteries to the vertebral column. Pseudoascension of these vessels was found to occur in association with the fetal age.

The arteries of the base of the brain in the N. American mink (Mustela vison (Brisson, 1756)).

110 brains of the N. American mink were studied for the arteries of the base of the brain, using the anatomical method and Digital Imaging Analysis. Two arterial circles were isolated: the larger cerebral circle (CC) and the smaller medullar circle (MC). These were connected by the basal artery of the brain. We found that in CC, its left part was larger, whereas in MC, it was the right part that was larger. Also, the capacity was larger in the caudal part of MC than in its rostral part.

The plantar muscle in human fetuses.

One hundred plantar muscles were studied and measured in fifty human fetuses from the 4th to 8th month of intra-uterine life. A reduction in the plantar muscle was observed due to slower development of the belly of muscle in relation to the tendon, which was as one to six (1:6). Mechanisms of reduction in the plantar muscle and in the long palmar muscle were compared in the study (5).

Hippocampus in the N. American mink (Mustela vison Brisson, 1756).

In sixty adult minks the hippocampus was dissected and measurements of its individual components were taken. Anatomical studies of the mink have been hardly undertaken, while the studies of the mink's brain can be considered as "terra incognita" (D. Goscicka). This is why it was decided to conduct an examination of the hippocampus of this animal.