Studying the formation of aggregates in recombinant human granulocyte-colony stimulating factor (rHuG-CSF), lenograstim, using size-exclusion chromatography and SDS-PAGE

The stability of proteins is a subject of intense current interest. Aggregation, as a dominant degradation pathway for therapeutic proteins, may cause multiple adverse effects, including loss of efficacy and immunogenicity. In the present study, the formation of aggregates in lenograstim under physiological conditions was monitored. For this purpose, a simple and selective size-exclusion high-performance liquid chromatography method for detection and separation of aggregates from intact protein was developed. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis was performed under reducing and non-reducing conditions to determine the nature of aggregate bond formation. Using both techniques, the presence of a low aggregate content attached via disulfide bonds was detected.     

Primary bone marrow lymphoma is a rare neoplasm with poor outcome: case series from single tertiary care centre and review of literature

Primary bone marrow lymphoma is a rare disease and remains undiagnosed due to deceptive clinical presentation. Here, we report four cases of primary bone marrow B‐cell non‐Hodgkin lymphoma, which presented with cytopenias without any lymphadenopathy or organomegaly. Bone marrow examination revealed large atypical B‐cells with a reactive T‐cell infiltrate with suppression of the normal hematopoietic elements. This lymphoma is known to have a poor prognosis. Inspite of treatment, two of our patients died during chemotherapy. Two patients relapsed, of which one showed an early relapse after two months and was put on an alternative regimen. The other patient relapsed twice at an interval of 4 and 5 years, respectively, following which he remained in remission for another 5 years and had recently shown a relapse for the third time. Review of literature revealed seven case series and 11 case reports of primary bone marrow lymphoma in the last five decades.     

Susceptibility for and clinical manifestations of rheumatoid arthritis are associated with polymorphisms of the TNF-alpha, IL-1beta, and IL-1Ra genes

OBJECTIVE: To analyze the association of genetic polymorphisms of pro-inflammatory cytokines with rheumatoid arthritis (RA) in comparison with healthy controls from Northern Sweden and the potential contribution of these genetic variants for disease severity and development of cardiovascular complications. METHODS: Polymerase chain reaction amplification was used for analysis of TaqI restriction fragment length polymorphism (RFLP) of interleukin-1 beta (IL-1beta), variable tandem repeat polymorphism of IL-I receptor antagonist (IL-1Ra) gene and NcoI RFLP at position -308 of tumor necrosis factor-alpha (TNF-alpha) gene. One hundred and fifty-four patients with RA, 42 men and 112 women, were consecutively recruited into the study through the Department of Rheumatology. RESULTS: The allele A1 of TNF-alpha was more common in the patient group (p < 0.01; OR = 1.62). Patients having the genotype A1A2 seemed to develop more severe disease compared with patients with A1A1 genotype: they were younger at disease onset (p < 0.05), had a higher accumulated disease activity (p < 0.05) and worse functional class (p < 0.05). Patients with genotype A2A2 of IL- 1beta had higher accumulated disease activity score than patients with A1A1 and A1A2 (p < 0.05). The allelic combination Al IL-1beta/A2 IL-1Ra was less prevalent in RA patients who developed cardiovascular complications (p < 0.005; OR = 0.20). CONCLUSIONS: The Al allele of TNF-alpha associates with RA. Genotypes A1A2 of TNF-alpha and A2A2 of IL-1beta are associated with more severe disease. The allelic combination A1IL-1beta/A2 IL-1Ra is less often present in RA patients who developed cardiovascular complications.     

Diastolic dysfunction in hypertension

Heart failure is one of the most common causes of cardiovascular morbidity and mortality, and hypertension is the most common cause of cardiac failure. Recent studies have shown that isolated diastolic dysfunction very often accompanies hypertensive heart disease. Ventricular diastolic function may be divided into an active relaxation phase and a passive compliance period. These two components have been investigated invasively, and they remain the gold standards for the study of diastolic function. However, in the routine clinical setting, echocardiographic and Doppler techniques are most useful for evaluating ventricular filling. Thus, analysis of E and A waves of mitral flow have provided important and useful information. Unfortunately, these indices depend on too many factors. Newer indices obtained from ventricular time intervals, tissue Doppler imaging, and color M-mode echocardiography have enhanced the means to assess diastolic function. In addition, new methods including MRI and cine CT have also provided better understanding of left ventricular filling in hypertension. Using these techniques, diastolic dysfunction has been found to be common in patients with hypertension, even before left ventricular hypertrophy is demonstrable and before hypertension in young, normotensive male offspring of hypertensive parents has developed. Furthermore, it has been made clear recently that myocardial ischemia and fibrosis are two important factors associated with diastolic dysfunction in hypertension.     

Morphology of Balkan endemic nephropathy: current state

Balkan endemic nephropathy (BEN) is interesting renal disease, because of its unique clinical, epidemiological and morphological characteristics: intensive interstitial fibrosis and tubular atrophy without any inflammation. In the present paper we evaluate the incidence of BEN from the morphological point of view for the last decade. Therefore we analyzed material obtained from autopsies, kidney biopsies and nephrectomy due to upper urothelial cancer (UUC) from the patients which were divided into two groups: those with permanent residence in BEN areas and those from nonendemic areas. At the Institute of Pathology, University of Belgrade for the last 15 years we had only 1 autopsy due to BEN out of 6,825. More than 30 years ago there were over 50 autopsy cases of BEN at the same institute. For the last decade we had only 2 kidney biopsies suspected for BEN out of 2,182, but morphologically not confirmed as BEN. However, previously we had over 40 kidney biopsies diagnosed as early or late stage of BEN. At the Clinical Center of Serbia 180 nephrectomies were performed due to UUC. The incidence of UUC for the last five years in BEN regions has significantly decreased, whereas at the same time in non-BEN regions it has remained on the same level. There was no morphological difference of the renal tissue adjacent to tumor between patients from BEN and non-BEN regions. According to our study based on routine pathological work, we could clearly conclude that BEN today is more clinical and epidemiological than a morphological entity.     

Prevalence of TMD among Children Provided with Fixed Orthodontic Treatment

BackgroundAccording to available scientific references and textbooks, there are contradictory views concerning the etiology of signs and symptoms of TMD.ObjectivesThe aim of this study was to determine a correlation between the incidence of signs and symptoms of TMD in children aged 12-18 who do not wear a fixed orthodontic appliance and the incidence of signs and symptoms of TMD in children who wear a fixed orthodontic appliance.Material and MethodsThe total number of 120 subjects were included in this survey and divided into two groups. There were 60 respondents in the experimental group that consisted of 30 boys and 30 girls with different types of malocclusion, who were treated with a fixed orthodontic straight wire technique. The remaining 60 respondents, which was a group that also consisted of 30 boys and 30 girls, were patients with neutroclusion.ResultsThe results of the study have shown that the TMJ clicking sound symptom, the most common symptom of TMD, occurs with almost equal prevalence in both groups of respondents; specifically, 56.4% in orthodontic patients, and 46.6% in the control group respondents. A statistically significantly higher percentage of female respondents in both groups have experienced headache problems (p <0.03).ConclusionOn the basis of the statistics obtained as a result of this research, we can come to the conclusion that there is no correlation between the fixed orthodontic treatment and the development of signs and symptoms of TMD.     

Antimicrobial resistance among Haemophilus influenzae isolates responsible for lower respiratory tract infections in Poland, 2005–2019

European Journal of Clinical Microbiology & Infectious Diseases - Haemophilus influenzae is a human-specific pathogen responsible for respiratory tract infections, meningitis, and sepsis. The...