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Przemysław Zdziarski

Publications and source records attributed to Przemysław Zdziarski.

9 recordsLinked to original sources

[Benzylpenicillin as an allosteric effector].

Benzylpenicillin (penicillin G) is a model drug for studies of drug-protein biochemical interactions. Furthermore the literature indicates that benzylpenicillin and protein conjugation is a universal phenomenon: benzylpenicillin is known to readily conjugate to proteins-serum albumin, globulin and others peptides to modify space structure and electrophoretical properties. The aim of the study was to test if the benzylpenicillin is an allosteric effector. Serum benzylpenicillin concentration in geometric progression was used. Then acid phosphatase (AcP), alanine aminotransferase (AIAT) activity and international normalized ratio (INR) was tested. Although benzylpenicillin influences AcP and INR, only AcP activity is directly proportional to the benzylpenicillin concentration (Pc): change of AcP activity was the derivative of Pc in 76% (R2 = 0.7635). Furthermore, the benzylpenicillin appears to be uncompetitive inhibitor of acid phosphatase (inhibitory constant Ki = 95.67M; Vmax = 34.843 nKat). On the contrary no effect of AIAT activity was observed. Unexpectedly INR was modified in irregular manner: in some concentrations of benzylpenicillin INR was over 25% lower than in control probe (INR approximately 0.6 vs. 0.82). Unfortunately INR > 6.5 is accepted as an early indicator of poor prognosis in fulminant hepatic failure. This phenomenon may be useful in sepsis as a prevention of disseminated intravascular coagulation (DIC). These data indicate that high benzylpenicillin concentration may be the cause of artifacts. The facts allow of interpretation that the allosteric effect of benzylpenicillin on enzymes activity is a possible mechanism of unpredictable adverse drug reactions (i.e. intolerance).

Allosteric Regulation↗

[Toxic shock syndrome as a result of opportunistic infection].

Toxic Shock Syndrome (TSS) is a potentially fatal illness caused by a particular strain of Staphylococcus aureus. The clinical presentation is similar to that of septic shock because of systemic inflammatory response syndrome-(SIRS). In the case report ineffective therapy of puerperal staphylococcal infection and its complication (reactive arthritis) with bacteriostatic and anti-inflammatory drug was described. 24 years old woman with puerperal infection was empirically treated with doxycycline. Fever and general weakness disappeared, but four weeks later gonarthritis with stiffening developed (reactive arthritis) treated with steroids plus amoxicillin-clavulanate. Unfortunately after regression of gonarthritis and steroid withdrawal TSS and SIRS suddenly occurred. It was successfully treated with penicillin plus gentamycin. In the history of TTS the infection and inflammation are closely interwoven: clinical recovery from immunocompromise is associated with the onset of SIRS. Further, bacterial growth occurs when inflammatory process was quite inhibited (by puerperium or steroids). The natural history of the TSS confirm that regression of inflammatory symptoms in infectious diseases (especially in SIRS) is not tantamount to recovery. Moreover, immunocompetence is main requirement of successful treatment with bacteriostatic agents.

Adult↗

[Medicine hypersensitivity--case report].

In this paper a case of good tolerance to benzathine benzylpenicillin, but benzylpenicillin potassium allergy in subject with history of multidrug hypersensitivity was described. The same therapeutic agent is contained in both commercial drugs and dosage formulation can cause the unpredictable adverse drug reactions (ADRs). This thesis was confirmed by positive intradermal test with the same, but negative with other commercial product of benzylpenicillin potassium. Later chromatographic analysis shows drug contaminations. Thus an exclusion of allergy to drug impurities (and additives) is necessary for correct diagnosis benzylpenicillin allergy (and any active constituent). Furthermore, allergy to drug impurities (and additives) closely resemble cross-reactions or multiple chemical sensitivity syndrome (MCSS).

Anti-Bacterial Agents↗

[Mild form of Lyell's syndrome as an consequence of inappropriate BCG revaccination--case report].

In this case report a rare adverse event (mild toxic epidermic necrolysis (Lyell)) was described. Incorrect a purified protein derivative (PPD) administration involves false negative tuberculin test (TT): BCG vaccine was injected even though high immunization to BCG. Mild, benign epidermic necrolysis, fever, mononucleosis-like syndrome, splenomegaly and lymphadenopathy were observed. Evaluation of white blood cells was done by automatic (simultaneously two analysers: Baker 900 plus and Technicon, Bayer) and by microscopic methods and revealed high lymphocyte activation (blastic transformation), lymphocytosis and high eosinophilia.. Wiener and coworkers describe interleukin-2-induced dermatotoxicity resembling toxic epidermal necrolysis. Further the most common side effects of IL-2 are skin eruptions and eosinophilia. Careful analysis yielded the conclusions that Lyell's syndrome may be fatal consequence of inappropriate revaccination, hyperergia--delayed type hypersensitivity and massive IL-2 release. Successful dexamethasone therapy confirms this observation.

Adolescent↗

Role of pencillin binding proteins in pencillin allergy.

All beta-lactam sensitive bacteria contain enzymatic penicillin binding proteins (PBPs), which are membrane-bound enzymes and targets of beta-lactam antibiotics. In this work evaluation of the significance of PBPs in immune response to benzylpenicillin was presented. 35 patients with allergic reactions to penicillin and 17 subjects without penicillin allergy, but exposed, were studied. Proliferative T-cell responses to benzylpenicillin, penicillin and PBPs conjugates (Pc-PBPs) from E. coli, K. oxytoca, S. aureus, S. epidermidis or serum protein (Pc-S) were measured. Although each allergic individual responds to Pc-PBPs in several different ways, specific proliferation of T lymphocytes with Pc-PBPs from bacterial membranes was significant higher than with Pc or Pc-S. This observation gives us a real insight into the causes of the drug allergy: individual allergic reaction and susceptibility to the drug is in strict correlation with bacterial infection. It seems likely that acylation of PBPs could be the trigger for primary immune response to the hapten benzylpenicillin.

Anti-Bacterial Agents↗

Overuse of high stability antibiotics and its consequences in public and environmental health.

In this paper the ecological aspects of widespread antibiotic consumption are described. Many practitioners, veterinarians, breeders, farmers and analysts work on the assumption that a antibiotics undergo spontaneous degradation. It is well documented that the indiscriminate use of antibiotics has led to the water contamination, selection and dissemination of antibiotic-resistant organisms, alteration of fragile ecology of the microbial ecosystems. The damages caused by the overuse of antibiotics include hospital, waterborne and foodborne infections by resistant bacteria, enteropathy (irritable bowel syndrome, antibiotic-associated diarrhea etc.), drug hypersensitivity, biosphere alteration, human and animal growth promotion, destruction of fragile interspecific competition in microbial ecosystems etc. The consequences of heavy antibiotic use for public and environmental health are difficult to assess: utilization of antibiotics from the environment and reduction of irrational use is the highest priority issue. This purpose may be accomplished by bioremediation, use of probenecid for antibiotic dosage reduction and by adoption of hospital infections methodology for control resistance in natural ecosystems.

Agriculture↗

[Difficulties with using T lymphocyte culture as a method for diagnosing allergies to benzylpenicillin].

The activation of T lymphocytes upon antigen stimulation plays a crucial role in adverse immune responses including drug-specific hypersensitivity reactions. The helpfulness of conventional tritiated thymidine incorporation assay for penicillin allergy diagnostics is limited. Benzylpenicillin, as a reactive compound, constitutes typical example of hapten. Most of research on penicillin hypersensitivity use benzylpenicillin-albumin (BPO-HSA) conjugates. Thus in this study we describe an in vitro proliferation assay with benzylpenicillin or penicillin and autologous serum protein conjugates. Interestingly these conjugates enhanced incorporation of tritiated thymidyne, when benzylpenicillin did not exert an influence on PBMCs proliferation (correlation coefficient r = -0.0119). This so-called carrier-effect indicates that benzylpenicillin and serum globulin complexes can take part in penicillin allergy (primary immune response). Optimal secondary response is obtained when the benzylpenicillin bind the same carrier for both primary and secondary immunization. Father-proliferation assay with modification of responses to phytohaemagglutinin by benzylpenicilloilated serum protein results in significant decrease of incorporation of [3H] thymidyne. Otherwise benzylpenicillin did not modify postmitogenic proliferation of PBMCs. Our findings indicate that the use of penicillin and autologous serum protein conjugates is helpful. This study show the manner in which benzylpenicillin forms T-cell epitopes.

Drug Hypersensitivity↗