Laparoscopic Surgery in the Treatment of Endometriosis

Endometriosis is a benign disease, which affects about 10% of reproductive age women and almost 50% of infertile women. Although every year at least 300 new articles deal with this topic, endometriosis is still a enigmatic disease starting with theories of etiopathogenesis where there is still no consensus about the major cause of endometriosis. Also there is still no consensus about the management of the disease, mainly when there is an infertile patient who is preparing for in vitro fertilization procedure

Priprava i evaluacija hidrogela s diazepamom za rektalnu primjenu

Diazepam (DZP) has become a commonly used drug for treatment of acute repetitive epileptic seizures and febrile convulsions in children. Considering the advantages of rectal administration of DZP, the objective of our study was to formulate and evaluate rectal hydrogels containing DZP as a drug substance in combination with suitable co-solvents and preservatives. Prepared HPMC (hydroxypropyl methylcellulose) hydrogels containing different concentrations of DZP (2, 4 and 6 mg mL-1) manifested good quality in respect to physico-chemical parameters (pH value, drug content, ingredients content and viscosity), antimicrobial efficiency and microbiological quality. Under the proposed HPLC conditions, satisfactory separation of DZP and the preservatives used was achieved. In vitro release studies have shown that the total amount of DZP was released in a period of 3 h. Prepared formulations were stable for four months at 26 oC (ambient temperature characteristic of the 2nd climate zone).Diazepam (DZP) je ljekovita tvar koja se upotrebljava u terapiji akutnih epileptičkih napada i febrilnih konvulzija u djece. U radu je opisana priprava i evaluacija hidrogela za rektalnu primjenu s diazepamom i odgovarajućim pomoćnim tvarima i konzervansima. Pripravci su sadržavali različite koncentracije DZP (2, 4 i 6 mg mL-1). Njihova fizičko-kemijska svojstva (pH vrijednost, sadržaj ljekovite i pomoćnih tvari, viskoznost), antimikrobna učinkovitost i mikrobiološka čistoća bili su zadovoljavajući. Razvijena je HPLC metoda kojom je postignuta separcija DZP i konzervansa. In vitro ispitivanja su pokazala da se cjelokupna količina DZP oslobodi tijekom 3 h. Pripravci su bili stabilni 4 mjeseca na temperaturi 26 C (sobna temperatura karakteristična za 2. klimatsku zonu)

Proučavanje stvaranja agregata rekombinantnog humanog granulocitnog faktora stimulacije kolonija (rHuG-CSF), lenograstima, pomoću kromatografije isključenjem prema veličini i 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.Stabilnost proteina vrlo je aktualna problematika. Agregacija, kao dominantni put razgradnje terapijskih proteina, može uzrokovati različite nuspojave, koje uključuju i gubitak učinkovitosti imunološkog sustava. U ovom radu praćeno je stvaranje agregata u lenograstimu pod fiziološkim uvjetima. Razvijena je jednostavna i selektivna tekućinska kromatografija visoke djelotvornost s isključenjem prema veličini za detekciju i razdvajanje agregata od intaktnog proteina. Pomoću natrij-dodecil sulfat poliakrilamidne gel elektroforeze u reducirajućim i nereducirajućim uvjetima utvrđen je način stvaranja agregata. Pomoću obje tehnike moguće je detektirati prisutnost malih količina agregata koji su spojeni disulfidnim vezama

The association of C3435T single-nucleotide polymorphism, Pgp-glycoprotein gene expression levels and carbamazepine maintenance dose in patients with epilepsy

The ABCB1 gene encodes the P-glycoprotein (Pgp) protein, which is thought to transport various antiepileptic drugs. The single nucleotide polymorphism (SNP) (C3435T) in exon 26 of this gene correlates with the altered expression levels of P-glycoprotein, range of drug response and clinical conditions. In order to investigate the influence of this polymorphism on the susceptibility to and efficacy of carbamazepine therapy, we evaluated the allelic frequency and genotype distribution of this variant in 162 epilepsy patients from the Republic of Macedonia. Statistically significant differences were detected neither in the allelic frequency and genotype distribution between carbamazepine-resistant and carbamazepine-responsive epilepsy patients nor between the subgroups of carbamazepine (CBZ)-responsive patients treated with different CBZ doses. However, the T-allele was enriched in CBZ-responsive patients who required higher maintenance CBZ doses, This observation was substantiated by the findings that the median total plasma levels were the lowest in patients with CC (20 μmol/L) followed by CT (23 μmol/L) and TT (29 μmol/L) genotypes. Patients with a CC genotype also had a higher likelihood of response compared to patients with CT or TT genotypes over a wide range (400–1000 mg/day) of initial doses of CBZ. The T allele showed a reduced expression of ~5% compared to the C allele in peripheral blood mononuclear cells in heterozygotes for the variant. This difference might be translated into ~10% difference in homozygotes for the variant, which would explain the trend towards a dose-dependent efficacy of the CBZ treatment in patients with different genotypes. A larger prospective study is warranted to clarify the clinical utility of a genotypespecific individualized CBZ therapy

Instabilities of proteins: theoretical aspects, degradation products and methods for their detection

Recombinant DNA technology has led to a significant increase in the number of peptide and protein based pharmaceuticals, giving a new approach to combat poorly controlled diseases. This particular development has been reached in the last two decades. However, proteins are highly susceptible of physical and chemical degradation resulting in a decrease or complete loss of biological activities. Reasons for their physical and chemical instabilities and the methods for their examination, become a challenge for the pharmaceutical scientists for successful development of stabile protein - based pharmaceuticals. The stability of protein - based pharmaceuticals is significant in terms of their pharmaceutical quality and biological activity. In addition, a right choice of suitable analytical methods is needed in order to detect an early formation of degradation products or modified forms

Analysis and critical review of ICH Q8, Q9 and Q10 from a generic pharmaceutical industry view point

Generic industry aims to produce safe, efficient, built-in quality medicines that will satisfy patients’ requirements and will be competitive on the market. In this paper, assessment of the need for quality by design (QbD) and process analytical technology (PAT) implementation by generic industry was made, by analysis of the ICH Q8, Q9 and Q10 guidelines and their implementation in European regulation. The review of the guidelines indicates differences in the life cycle of a generic medicine, leading to a final conclusion in terms of generic industry. PAT provides statistical analysis and real time quality monitoring, as the basis for proactive quality management. Using QbD/PAT, quality is proved and improved throughout the entire life cycle. Better understanding of the product and processes within a defined design space leads to easier proof of built-in quality throughout the life cycle of the medicine, faster and easier regulatory evaluation, faster time to market, as well as post marketing savings regarding costs and time. Implementation of QbD/PAT as a systematic approach together with risk assessment as part of quality management system is a useful challenge to the generic industry and gives an opportunity for technological, temporal, financial and quality improvement. It was concluded that having in mind its’ own manufacturing capabilities the applicant should optimize the implementation of QbD in accordance with current good manufacturing practice guidelines. Implementation of QbD/PAT is an innovative challenge for the generic industry. Managing pharmaceutical quality system allows the top management to make right decisions at the right time

Medical device risk management and its economic impact

The importance of medical devices in everyday users/patients lives is imensse. This is the reason why emphasis must be put on safety during their use. Satisfactory safety level can be achived by implementation of quality and risk management standards. Medical device manufacturers must learn to deal with the potential risks by using theoretical and practical examples and measures in order to protect their users/patients and themselves from suffering huge losses arising from adverse events or recall of their products. The best moment for implementation of risk management methods and analysis begins from the device design and development through manufacturing, sales and distribution. These way medical device manufacturers will succseed in protecting their users/patients from serious adverse events and at the same time protect their brand and society status, while minimizing economic losses