Synthesis and antitumor properties of amino acids acylated with 2-methyl-3-oxo-1-phenyl-1cyclopentane carboxylic acid

Acylation of the silyl esters of amino acids, specifically glycine, f-alanine, sarcosine, glycylglycine, and 6-aminopenicillanic acid, with 1-phenyl-3-oxo-2-methyl-1-cyclopentane carboxylic acid chloride yielded new analogs of the known antitumor antibiotic sarcomycin. The resulting compounds had high levels of antitumor activity.     

Aripiprazole-induced syndrome of inappropriate antidiuretic hormone secretion (SIADH)

Aripiprazole is a newer atypical antipsychotic agent used for effective treatment of schizophrenia. It significantly reduces unwanted side effects of older typical antipsychotics by targeting, with high affinity, dopamine D2/D3 and serotonin 5-HT1A/5-HT-2A receptors. Its documented mechanism of action makes it an unlikely agent to cause syndrome of inappropriate antidiuretic hormone secretion (SIADH). We present the first reported case of SIADH caused by aripiprazole in a patient with history of schizophrenia without other precipitating factors to explain hyponatremia or SIADH.     

Surgery in patients with haemophilia and high responding inhibitors: Izmir experience

Summary. This report evaluates the haemostatic efficacy of recombinant factor VIIa (rFVIIa) and activated prothrombin complex concentrate (APCC) in patients with haemophilia and high responding inhibitors who underwent major and minor surgery. Data pertaining to surgeries from 2001 to 2009 at a single centre were retrospectively analysed. During this period, 53 surgical procedures were performed in 30 haemophiliacs with high responding inhibitors. Mean age was 16.2 ± 9.4 years. Eleven major surgeries in 4 patients, 41 radioisotope synovectomies (RS) and one circumcision classified as minor surgery in 28 patients were performed. Among the major surgery procedures, four were treated with rFVIIa, five with APCC and two with sequential use of APCC and rFVIIa. We used rFVIIa at the dosage of 80–120 μg kg^?1 every 2 h and APCC 100 IU kg^?1 every 12 h for the major surgery. When performing RS, we used rFVIIa in 18 patients with 26 target joints and APCC in 9 patients with 15 target joints. Three consecutive doses of rFVIIa (90 μg kg^?1) were used at 2‐h intervals followed by additional three doses at 6‐h intervals. The initial dose of APCC was 75 IU kg^?1 followed by a second and third dose of 50 IU kg^?1 at 12‐h intervals. APCC and rFVIIa demonstrated excellent efficacy in our major and minor surgical interventions [100% (22/22) and 94% (31/33), respectively]. We had only two bleeding complications with rFVIIa. There were no thromboembolic complications. APCC and rFVIIa provide an effective and safe first line haemostatic therapy for inhibitor‐positive haemophiliacs, allowing both major and minor surgery to be successfully performed.     

Mean platelet volume in patients with rheumatoid arthritis: the effect of anti-TNF-alpha therapy

A number of mediators are involved in the inflammatory processes that affect joints and vascular wall of patients with rheumatoid arthritis (RA). Tumour necrosis factor alpha (TNFa) is one such mediator, and it is widely regarded as an important target for anti-rheumatic treatment. Most recent studies show that anti-TNFa medication suppresses inflammation and reduces overall activity of RA. The aim of the current study was to investigate changes of mean platelet volume (MPV) in response to the 3-month anti-TNFa therapy in RA. Twenty-one RA patients without established cardiovascular disease were recruited for anti-TNFa therapy and underwent thorough clinical and laboratory evaluation at baseline, 2 weeks, and 12 weeks. Anti-TNFa therapy resulted in a significant (p = 0.01) increase in MPV over the duration of the study (7.7 ± 0.9, 7.8 ± 1.1, and 8.4 ± 1.1 fL at baseline, 2 weeks, and 12 weeks, respectively). The results of the study expand perspectives of the use of MPV in conditions associated with high-grade inflammation, particularly RA, for monitoring anti-inflammatory treatment. More prospective studies with large numbers of patients are warranted to ascertain associations of high and low values of MPV with diverse markers of inflammation and vascular pathology.     

Patient resources in the therapeutic education of haemophiliacs in France: their skills and roles as defined by consensus of a working group

Summary. The activities of ‘expert patients’ or ‘patient tutors’, who help educate their peers, are gaining recognition in the health care system. This study investigates the role played by such patients in therapeutic education programmes organized by caregivers to validate the role of patients in implementing the therapeutic education of haemophilic patients and to define the skills required for such activities. This study employs the consensus methodology recommended by France’s National Authority for Health. The working group includes seven caregivers from Hemophiliac Treatment Centers (HTCs) and three patients from the French Association of Hemophiliacs (FAH). The role of patients in haemophilia education is recognized. Patients participating in the education of their peers are referred to as ‘patient resources’. A patient resource should be an adult, a volunteer and live in the same region as his peers. Candidates are chosen by the FAH and the HTCs to serve based on their motivation to facilitate the education of other patients as well as on their psychological and pedagogical aptitudes. A patient resource participates in the conception and administration of therapeutic education programmes. He also mediates between the caregivers and the patients. He ensures that the patients understand the material and are able to apply their knowledge in daily life. His activities are governed by professional ethics. Seven categories of skills were defined, permitting the group to determine precisely which skills are required to function as a patient resource. Supervision of the patients is planned to reinforce reflexive practices in the patients. Evolution of the health care system has led patients to become involved in therapeutic education. This phenomenon calls for a framework to be developed and an evaluation of its eventual effects.     

Synthesis and pharmacological activity of 1-(4-substituted phenyl)-1-alkyl(aryl)-3-piperidinopropanol hydrochlorides

Aminomethylation of substituted acetophenones with paraformaldehyde and piperidine hydrochloride yielded 4-substituted β-piperidinopropiophenones. Interaction of compounds I with the Grignard reagents in ether yielded 1-(4-substituted phenyl)-1-alkyl(aryl)-3-piperidinopropanols. The anti-inflammatory, analgesic, antipyretic, central m-cholinoblocking, and peripheral n-cholinoblocking actions of 1-(4-substituted phenyl)-1-alkyl(aryl)-3-piperidinopropanol hydrochlorides were studied. The study compounds were found to have marked central m-cholinoblocking and peripheral n-cholinoblocking activities. Only 1-(4-methoxyphenyl)-1-cyclohexyl-3-piperidinopropanol hydrochloride had anti-inflammatory activity.     

Synthesis and Biological Activity of Diaryl-Substituted 3-Morpholinopropanols

A series of 1-(4-substituted phenyl)-1-alkyl-2-phenyl-3-morpholinopropanols (I) have been synthesized via the interaction of 4-substituted α-phenyl-β-morpholinopropiophenones with Grignard's reagents in ether. The antiinflammatory and analgesic (non-narcotic) properties of the synthesized compounds have been evaluated. The most pronounced analgesic (non-narcotic) activity was observed for aminopropanols with 1-isoalkyl (isopropyl, isobutyl, isoamyl) radicals. __________ Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 39, No. 7, pp. 23 – 25, July, 2005.     

Synthesis,Antibacterial and Antitumor Activity of Semisynthetic Penicillins and Cephalosporins Based on New Sarcomycin Analogs

A series of new semisynthetic penicillins and cephalosporins containing structural fragments of the well-known antitumor antibiotic sarcomycin have been synthesized and their antitumor and antibacterial properties have been studied. The synthesized compounds showed substantial antitumor and antibacterial activities.__________Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 39, No. 2, pp. 13 – 15, February, 2005.     

Post-COVID syndrome: pulmonary complications

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected millions of people worlwide and caused a pandemic that is still ongoing. The virus can cause a disease named as COVID-19, which is composed of multi systemic manifestations with a pulmonary system predominance. As the time passes, we are dealing more and more with a wide variety of effects and complications of the disease in survivors as far as with concerns about the clinical outcome and the timeline of symptoms in different patients. Since the lungs are the most involved organs and the post-COVID prolonged and persistent effects are mainly related to the pulmonary system, it is crucial to define and predict the outcome and to determine the individuals that can progress to fibrosis and loss of function of lungs. This review summarizes the current literature regarding the pulmonary complications in post-COVID syndrome and the management of these conditions.     

Measurement of family impact of skin disease: further validation of the Family Dermatology Life Quality Index (FDLQI)

Aim To adapt the Impact on Family scale (IOF), originally developed for families of children with chronic illnesses, for use in families of adult patients and to examine the convergent validity of the Family Dermatology Life Quality Index (FDLQI) by comparing it with the adapted version of the IOF scale. Methods Adult family members of patients with different skin diseases attending the out‐patients clinic of a secondary referral centre completed the FDLQI and the adapted version of the IOF scale, whereas patients completed the Dermatology Life Quality Index (DLQI). Results A total of 50 patients and 50 family members/partners participated in the study. The mean scores for the three instruments were as follows: FDLQI = 6.0 (SD = 6.4, median = 4); IOF scale = 27.9 (SD = 8.2, median = 29); DLQI = 5.4 (SD = 5.6, median = 3). There was no difference between male and female participants in the mean scores of any of the three instruments. The FDLQI demonstrated high internal consistency (Cronbach's α = 0.91). Factor analysis revealed the presence of one factor structure underlying the items of the FDLQI, which explained 55.8% of the total variance. The IOF scale also showed a high internal consistency (Cronbach's α = 0.89). The results of factor analysis revealed one dominant factor and three weaker factors, which together explained 72% of the total variance. The convergent validity of the FDLQI was demonstrated by a highly significant positive correlation between the mean FDLQI and the IOF scale scores (r_s = 0.61, P < 0.0001). All the items of the FDLQI also had significant correlations with the mean total IOF scale scores (P < 0.05). Conclusions The results of this study have demonstrated that with minor modifications IOF scale, which was originally developed for families of children suffering from chronic illnesses, can also be used in families of adult dermatology patients. The study has also provided further evidence of the validity of the newly developed FDLQI.